The menace of obesity to depression and anxiety prevalence
Open accessAbstract
The incidence of depression and anxiety is amplified by obesity. Mounting evidence reveals that the psychiatric consequences of obesity stem from poor diet, inactivity, and visceral adipose accumulation. Resulting metabolic and vascular dysfunction, including inflammation, insulin and leptin resistance, and hypertension, have emerged as key risks to depression and anxiety development. Recent research advancements are exposing the important contribution of these different corollaries of obesity and their impact on neuroimmune status and the neural circuits controlling mood and emotional states. Along these lines, this review connects the clinical manifestations of depression and anxiety in obesity to our current understanding of the origins and biology of immunometabolic threats to central nervous system function and behavior.
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that obesity raises the risk of depression and anxiety mainly through immunometabolic and neuroinflammatory consequences of poor diet, inactivity, and visceral adiposity, rather than body weight alone. It synthesizes human epidemiological and rodent mechanistic evidence linking adipose and gut inflammation, neuroinflammation, neuroplastic and monoamine changes, and endocrine dysfunction to mood disorders.
Key findings
- Obesity increases depression risk: a meta-analytic overview cited by the review reports that obese adults self-reporting symptoms have 23–36% increased odds of developing depressed mood versus nonobese controls, while clinically diagnosed MDD is elevated by 14–34%; obese adolescents have a 40% increased risk of being depressed.
- Obesity also increases anxiety risk: the review states obesity heightens the odds of an anxiety disorder or anxiety symptoms by 30% and 40%, respectively, with a stronger relationship for severe obesity (BMI ≥ 35); diabetes is associated with a 48% greater likelihood of anxiety symptoms and a 20% higher risk of developing an anxiety disorder.
- Sex and metabolic status matter: depression and anxiety disorder diagnoses are approximately double for obese women compared with obese men, and metabolically healthy obese individuals show either no increased risk or a modest elevated risk of depression diagnosis versus nonobese controls.
- Proposed mechanisms include saturated fat and sugar intake, visceral adipose expansion, gut dysbiosis, peripheral inflammation (e.g., CRP, IL-6, TNFα), insulin and leptin resistance, HPA dysregulation, neuroinflammation, altered corticolimbic circuits, monoamine imbalances, and reduced hippocampal neurogenesis.
Methods
- Narrative review; no primary data collection, systematic search, or meta-analysis is reported.
- Synthesizes clinical and epidemiological observations with rodent models of diet-induced obesity, high-fat/high-sugar feeding, and depressive- or anxiety-like behaviors.
- Main analysis is qualitative integration of evidence across immunometabolic, neuroinflammatory, neural circuit, monoamine, and endocrine domains.
Limitations
- Stated: the causal relationship of diet-induced obesity to depression and anxiety in human studies is indirect; the literature linking inflammation to anxiety is much sparser; microbiota alterations across studies are conflicting and mechanisms remain unclear; the precise contribution of HPA activity and insulin’s role in mood circuits remain to be established; and it remains poorly understood to what degree particular changes are causal or a consequence of mood and metabolic changes.
- Stated: human leptin studies are limited, and evidence for depression and obesity comorbidity is described as limited in the concluding remarks.
- Evident: as a narrative review, it does not systematically quantify or appraise the evidence, and much mechanistic support comes from rodent models, so human causality and effect sizes are not established by this paper itself.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 136 cited sources checked · 0 supported · 0 flagged
- Premisecitation§ Epidemiology and clinical features
Obese adolescents have a 40% increased risk of being depressed.
“Emphasizing the importance of early detection and treatment, a longitudinal meta-analysis suggests that obese adolescents have a 40% increased risk of being depressed [19].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [19] source
Not checked in the free run.
- Premisecitation§ Epidemiology and clinical features
Obese adults self-reporting symptoms have 23-36% increased odds of developing depressed mood as compared with nonobese controls.
“A meta-analytic overview illustrates that obese adults self-reporting symptoms have 23-36% increased odds of developing depressed mood as compared with nonobese controls, whereas clinically diagnosed MDD is elevated by 14-34% [2].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [2] source
Not checked in the free run.
- Premisecitation§ Convergence of mood and metabolic deficits
Obesity is coupled to structural and functional brain changes that are remarkably similar to those observed in depressive disorders, such as region-specific increases in cell density and compromised neural connectivity and excitability.
“Obesity is coupled to various structural and functional changes in the brain that are remarkably similar to those observed in depressive disorders, such as regionspecific increases in cell density and compromised neural connectivity and excitability [5,6].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Convergence of mood and metabolic deficits
The odds of developing major depressive disorder and anxiety increase as a function of the number of coexisting metabolic impairments, such as those characteristic of metabolic syndrome.
“The odds of developing major depressive disorder (MDD) and anxiety increase as a function of the number of coexisting metabolic impairments, such as those characteristic of metabolic syndrome [3,4].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ Epidemiology and clinical features
Obesity heightens the odds of anxiety symptoms by 40%.
“A similar positive relationship is observed with anxiety: obesity heightens the odds of an anxiety disorder or anxiety symptoms (e.g., dread, unease) by 30% and 40%, respectively [1,20].”
Quote in the paperNot a substantial claim0 of 2 sources checked
- Premisecitation§ Epidemiology and clinical features
Waist-to-hip ratio provides a better estimate of visceral adiposity and metabolic dysfunction than BMI.
“The odds of depression are higher when evaluating the waist-to-hip ratio [16,17] which provides a better estimate of visceral adiposity and metabolic dysfunction than BMI [18].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] source
Not checked in the free run.
- Interpretationnone given§ The menace of obesity to depression and anxiety prevalence
The psychiatric consequences of obesity stem from poor diet, inactivity, and visceral adipose accumulation.
“Mounting evidence reveals that the psychiatric consequences of obesity stem from poor diet, inactivity, and visceral adipose accumulation.”
Quote in the paperNot a substantial claim - Premisecitation§ Epidemiology and clinical features
Atypical depression has stronger links to peripheral and central inflammation.
“This form of depression has stronger links to peripheral [10,11] and central [12] inflammation.”
Quote in the paperNot a substantial claim0 of 3 sources checked - Premisecitation§ Convergence of mood and metabolic deficits
Elevated body mass index is predictive of a chronic course of depressive and anxiety symptoms.
“An elevated body mass index (BMI) is predictive of a chronic course of depressive and anxiety symptoms [1,2].”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning§ The menace of obesity to depression and anxiety prevalence
The incidence of depression and anxiety is amplified by obesity.
“The incidence of depression and anxiety is amplified by obesity.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Convergence of mood and metabolic deficits
Prolonged inflammation caused by poor dietary lifestyle and inactivity and resulting metabolic consequences are required for obesity-related brain changes and depressive and anxiety outcomes.
“Several lines of evidence suggest that prolonged inflammation caused by poor dietary lifestyle and inactivity and resulting metabolic consequences are required for such outcomes.”
Quote in the paperNot a substantial claim- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisecitation§ Epidemiology and clinical features
Clinically diagnosed major depressive disorder is elevated by 14-34% in obese adults as compared with nonobese controls.
“A meta-analytic overview illustrates that obese adults self-reporting symptoms have 23-36% increased odds of developing depressed mood as compared with nonobese controls, whereas clinically diagnosed MDD is elevated by 14-34% [2].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [2] source
Not checked in the free run.
- Interpretationreasoning§ Convergence of mood and metabolic deficits
Obesity increases the incidence of depression and anxiety as a function of the extent of metabolic dysfunction.
“Obesity increases the incidence of depression and anxiety as a function of the extent of metabolic dysfunction.”
Quote in the paperSubstantial claim - Premisecitation§ Epidemiology and clinical features
Obesity heightens the odds of an anxiety disorder by 30%.
“A similar positive relationship is observed with anxiety: obesity heightens the odds of an anxiety disorder or anxiety symptoms (e.g., dread, unease) by 30% and 40%, respectively [1,20].”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Epidemiology and clinical features
Obese individuals, particularly those presenting attributes of metabolic syndrome, tend to develop the atypical subtype of depression.
“Obese individuals, particularly those presenting attributes of metabolic syndrome (abdominal obesity, hyperglycemia, hypertension, elevated triglycerides), tend to develop the atypical subtype [9] (Box 1).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [9] source
Not checked in the free run.
- Interpretationreasoning§ The menace of obesity to depression and anxiety prevalence
Metabolic and vascular dysfunction resulting from obesity, including inflammation, insulin and leptin resistance, and hypertension, are key risks to depression and anxiety development.
“Resulting metabolic and vascular dysfunction, including inflammation, insulin and leptin resistance, and hypertension, have emerged as key risks to depression and anxiety development.”
Quote in the paperSubstantial claim - Premisecitation§ Box 1. Sex, gender, and metabolic risks
Obese individuals characterized as metabolically healthy present either no increased risk or a modest elevated risk of depression diagnosis as compared with nonobese controls.
“In a consistent manner, obese individuals characterized as metabolically healthy (normal blood pressure, C-reactive protein, triglycerides, and glycaemia) present either no increased risk [161] or a modest elevated risk [3] of depression diagnosis as compared with nonobese controls.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Food environment and nutrient actions
Poor diet, inflammation, and depressive symptomology are linked.
“Several lines of evidence link poor diet, inflammation, and depressive symptomology [21,22].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [21]
Not checked in the free run.
- cites [22] source
Not checked in the free run.
- Premisecitation§ Box 1. Sex, gender, and metabolic risks
Diabetes is associated with a 20% higher risk of developing an anxiety disorder.
“Diabetes is associated with a 48% greater likelihood of anxiety symptoms and a 20% higher risk of developing an anxiety disorder [20].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] source
Not checked in the free run.
- Interpretationreasoning§ Food environment and nutrient actions
The collective central actions of saturated dietary fats to decrease polyunsaturated fatty acid phospholipid-derived metabolites and increase proinflammatory signaling is a culprit in the development of depression and anxiety in obese individuals.
“The collective central actions of saturated dietary fats to decrease PUFA phospholipid-derived metabolites and increase proinflammatory signaling looms large as a culprit in the development of depression and anxiety in obese individuals.”
Quote in the paperSubstantial claim- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisecitation§ Epidemiology and clinical features
There is a stronger relationship between severe obesity (BMI ≥ 35) and anxiety.
“Indeed, there is a stronger relationship between severe obesity (BMI ≥ 35) and anxiety [1].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Prolonged saturated fat intake can interfere with energy homeostasis by stimulating visceral adipose deposition and inflammation in humans.
“Prolonged saturated fat intake can interfere with energy homeostasis by stimulating visceral adipose deposition and inflammation in humans [23] and impairing central leptin and insulin signaling in rodents [24,25].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] source
Not checked in the free run.
- Premisecitation§ Box 1. Sex, gender, and metabolic risks
Adiposity serves as a better predictor of depression than body weight in women than in men.
“Adiposity serves as a better predictor of depression than body weight in women than in men [149].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [149] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Increased dietary n-3 intake can improve insulin sensitivity.
“Increased dietary n-3 intake can improve insulin sensitivity [43] and significantly diminish plasma CRP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) levels in humans [44].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [43] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
EPA and DHA limit the inflammatory effect of eicosanoids derived from arachidonic acid.
“Both EPA and DHA limit the inflammatory effect of eicosanoids derived from arachidonic acid, an omega-6 fatty acid with plasma levels that positively correlate with MDD severity and reduced serotonin transporter binding in the brain [50].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [50] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Higher n-3 consumption is linked with lower prevalence and severity of mood disturbances in humans.
“Several reports link higher n-3 consumption with lower prevalence and severity of mood disturbances in humans [45] and demonstrate that n-3 supplementation dampens neuroinflammation and attenuates behavioral indices of mood deficits in rodents [46,47].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] source
Not checked in the free run.
- Premisecitation§ Box 1. Sex, gender, and metabolic risks
Women with depression and anxiety are more likely to have increased appetite and weight gain than male counterparts.
“Women with depression and anxiety are more likely to have increased appetite and weight gain than male counterparts [150], an outcome associated with the effects of stress to stimulate palatable food intake [119].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [150] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Prolonged intake of high sucrose or fructose diets can induce anxiety- and depressive-like behaviors and motivational deficits in rodents.
“While sugar consumption can alleviate stress and pain and improve negative mood and emotional states in the short-term [52], prolonged intake of high sucrose or fructose diets can induce anxiety-and depressive-like behaviors and motivational deficits [53][54][55], effects that are more pronounced during the adolescent period [55][56][57].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [53] source
Not checked in the free run.
- cites [54] source
Not checked in the free run.
- cites [55] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisecitation§ Food environment and nutrient actions
Brain transport of fatty acids is elevated in individuals with metabolic syndrome.
“Brain transport of fatty acids is elevated in individuals with metabolic syndrome [48].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [48] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Increased dietary n-3 intake can significantly diminish plasma CRP, interleukin-6, and tumor necrosis factor alpha levels in humans.
“Increased dietary n-3 intake can improve insulin sensitivity [43] and significantly diminish plasma CRP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) levels in humans [44].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44]
Not checked in the free run.
- Interpretationcitation§ Food environment and nutrient actions
Changes in brain fatty acid composition are likely one means by which saturated dietary fats generate neuroinflammatory responses and mood deficits.
“Moreover, chronic saturated high-fat feeding increases saturated fatty acid levels and appreciably decreases PUFA levels in the brain of rodents [49], changes that are likely one means by which saturated dietary fats generate neuroinflammatory responses and mood deficits.”
Quote in the paperNot a substantial claim- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisecitation§ Box 1. Sex, gender, and metabolic risks
The prevalence of major depressive disorder is nearly twice as high in people with type 2 diabetes as in those without.
“Correspondingly, the prevalence of MDD is nearly twice as high in people with type 2 diabetes [159] and more than threefold higher in people with type 1 diabetes than those without, with greater rates in diabetic women than men [160].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [159] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Central GPR120 agonism can suppress anxiety-like behaviors in mice exposed to a saturated high-fat diet.
“Correspondingly, central GPR120 agonism can suppress anxiety-like behaviors in mice exposed to a saturated HFD [51].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [51] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisecitation§ Box 1. Sex, gender, and metabolic risks
Diabetes is associated with a 48% greater likelihood of anxiety symptoms.
“Diabetes is associated with a 48% greater likelihood of anxiety symptoms and a 20% higher risk of developing an anxiety disorder [20].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Prolonged high-fat diet triggers neurobehavioral deficits associated with blunted mesolimbic dopamine function in rodents.
“To this end, rodent research has revealed that prolonged high-fat diet (HFD) elicits metabolic dysfunction and increases anxiety-and depressive-like behaviors [28][29][30][31][32][33][34][35][36], heightens stress and hypothalamic-pituitary-adrenal (HPA) responses [37,38], and triggers neurobehavioral deficits associated with blunted mesolimbic dopamine function [39][40][41].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [39] source
Not checked in the free run.
- cites [40] source
Not checked in the free run.
- cites [41] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Interpretationreasoning§ Food environment and nutrient actions
The causal relationship of diet-induced obesity to depression and anxiety development in human studies is indirect.
“The causal relationship of diet-induced obesity (DIO) to depression and anxiety development in human studies is indirect.”
Quote in the paperNot a substantial claim - Premisecitation§ Box 1. Sex, gender, and metabolic risks
The sex distinction in incidence of depression and anxiety narrows considerably in conditions of severe obesity (BMI ≥ 40).
“This sex distinction in incidence narrows considerably in conditions of severe obesity (BMI ≥ 40) [1].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [1] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Prolonged saturated fat intake can impair central leptin and insulin signaling in rodents.
“Prolonged saturated fat intake can interfere with energy homeostasis by stimulating visceral adipose deposition and inflammation in humans [23] and impairing central leptin and insulin signaling in rodents [24,25].”
Quote in the paperNot a substantial claim0 of 2 sources checked- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisecitation§ Box 1. Sex, gender, and metabolic risks
The frequency of depression and anxiety disorder diagnoses is approximately double for obese women as compared with obese men.
“The frequency of depression and anxiety disorder diagnoses are approximately double for obese women as compared with obese men [1,157], a divergence that corresponds with lifetime prevalence independent of body weight.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Box 1. Sex, gender, and metabolic risks
In both sexes, negative mood state is more robustly associated with metabolic impairments such as inflammation, hypertension, and insulin resistance rather than body weight itself.
“In both sexes, negative mood state is more robustly associated with metabolic impairments such as inflammation, hypertension, and insulin resistance rather than body weight itself [3].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Prolonged high-fat diet heightens stress and hypothalamic-pituitary-adrenal responses in rodents.
“To this end, rodent research has revealed that prolonged high-fat diet (HFD) elicits metabolic dysfunction and increases anxiety-and depressive-like behaviors [28][29][30][31][32][33][34][35][36], heightens stress and hypothalamic-pituitary-adrenal (HPA) responses [37,38], and triggers neurobehavioral deficits associated with blunted mesolimbic dopamine function [39][40][41].”
Quote in the paperSubstantial claim0 of 2 sources checked- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Interpretationreasoning§ Food environment and nutrient actions
These outcomes appear to largely stem from the immune-stimulating properties of excess fat intake that propagate metabolic and vascular disturbances and enhance neuroinflammation.
“These outcomes appear to largely stem from the immune-stimulating properties of excess fat intake that propagate metabolic and vascular disturbances and enhance neuroinflammation.”
Quote in the paperSubstantial claim- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisecitation§ Food environment and nutrient actions
Membrane n-3 composition is blunted in individuals with mood disorders.
“Indeed, membrane n-3 composition is blunted in individuals with mood disorders, a finding that gave rise to the phospholipid PUFA hypothesis of depression [50].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [50] source
Not checked in the free run.
- Premisecitation§ Inflammatory conduits to the brain
Inflammatory interventions can lead to symptoms of depression and anxiety, such as in patients receiving interferon alpha treatment.
“Additional evidence contributing to neuroimmune theories of depression and anxiety arise from observations that inflammatory interventions can lead to symptoms of these disorders, such as in the case of patients receiving interferon (IFN) alpha treatment [64].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [64] source
Not checked in the free run.
- Premisecitation§ Gut dysbiosis
Persistent peripheral inflammation, even if low-grade, can elicit sustained neuroinflammatory actions that ultimately generate changes in brain structure, connectivity, and excitability.
“However, persistent peripheral inflammation, even if low-grade, can elicit sustained neuroinflammatory actions that ultimately generate changes in brain structure, connectivity, and excitability [61].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [61] source
Not checked in the free run.
- Premisecitation§ Adipose expansion
Prolonged saturated high-fat feeding that does not lead to significant adipose deposition fails to stimulate anxiety-like behaviors in rodents.
“The importance of excessive adipose mass to emotional deficits in obesity is highlighted by rodent studies showing that prolonged saturated high-fat feeding that does not lead to significant adipose deposition fails to stimulate anxiety-like behaviors [37,38].”
Quote in the paperSubstantial claim0 of 2 sources checked- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisenone given§ Adipose expansion
The production of proinflammatory cytokines by white adipose tissue is a major source of obesity-related inflammation.
“The production of proinflammatory cytokines by white adipose tissue is a major source of obesity-related inflammation.”
Quote in the paperSubstantial claim - Premisecitation§ Inflammatory conduits to the brain
Depression in a subgroup of individuals is associated with elevated circulating levels of proinflammatory cytokines, chemokines, and cell adhesion molecules, as well as prostaglandins and other arachidonic acid derivatives.
“Depression in a subgroup of individuals is associated with elevated circulating levels of proinflammatory cytokines, chemokines, and cell adhesion molecules, as well as prostaglandins and other arachidonic acid derivatives [61].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [61] source
Not checked in the free run.
- Premisecitation§ Gut dysbiosis
Chronic changes in microbiota composition in obesity (dysbiosis) are associated with inflammation, insulin resistance, and mental health deficits.
“Chronic changes in microbiota composition in obesity (dysbiosis) are associated with inflammation, insulin resistance, and mental health deficits [72].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [72] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
The effects of prolonged high sugar intake on anxiety- and depressive-like behaviors are more pronounced during the adolescent period.
“While sugar consumption can alleviate stress and pain and improve negative mood and emotional states in the short-term [52], prolonged intake of high sucrose or fructose diets can induce anxiety-and depressive-like behaviors and motivational deficits [53][54][55], effects that are more pronounced during the adolescent period [55][56][57].”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [55] source
Not checked in the free run.
- cites [56] source
Not checked in the free run.
- cites [57] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisecitation§ Gut dysbiosis
Suppression of microglia and astrocyte reactivity is implicated in the response to antidepressant therapies.
“Consistently, suppression of microglia [80] and astrocyte [81] reactivity is implicated in the response to antidepressant therapies.”
Quote in the paperNot a substantial claim0 of 2 sources checked - Premisecitation§ Food environment and nutrient actions
Brain glucose transport and metabolism can be both increased or decreased by obesity, depending upon the structure under investigation.
“Brain glucose transport and metabolism can be both increased or decreased by obesity, depending upon the structure under investigation [59].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [59] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
Reductions in glucose uptake in the hippocampus have been connected to cognitive deficits in obesity.
“Reductions in glucose uptake in the hippocampus have been connected to cognitive deficits in obesity [59].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [59] source
Not checked in the free run.
- Interpretationreasoning§ Gut dysbiosis
The inflammatory consequences of dysbiosis are well-positioned to contribute to psychiatric and neurological comorbidities of obesity.
“The mechanisms by which gut microbiota regulate brain function remain unclear; however, the inflammatory consequences of dysbiosis are well-positioned to contribute to psychiatric and neurological comorbidities of obesity.”
Quote in the paperNot a substantial claim- Rests on an assumption: Gut microbiota alterations observed in diet-induced obese mice translate to human obesity-related mood dysfunction.
- Interpretationreasoning§ Food environment and nutrient actions
The nature and amount of dietary fat and sugars consumed can have a potent influence on metabolic and mental health.
“It is nonetheless clear from the collection of studies examining the influence of diet and nutrients, that the nature and amount of dietary fat and sugars consumed can have a potent influence on metabolic and mental health.”
Quote in the paperSubstantial claim- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Premisecitation§ Gut dysbiosis
Microbiota alterations mediate diet-induced parental programming of offspring neurobehavioral function and mood disorder susceptibility.
“In addition, mounting evidence suggests that microbiota alterations mediate diet-induced parental programming of offspring neurobehavioral function and mood disorder susceptibility [71].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [71] source
Not checked in the free run.
- Premisecitation§ Adipose expansion
Resident macrophages and T-lymphocyte immune cells perpetuate the inflammatory situation in adipose tissue.
“It is namely resident macrophages and T-lymphocyte immune cells that perpetuate the inflammatory situation in adipose tissue [68], and dietary saturated fatty acids can be a direct source of metabolic stress that can promote inflammation by increasing TLR4 signaling.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [68] source
Not checked in the free run.
- Premisecitation§ Food environment and nutrient actions
The presence of excess sugar in a high-fat diet was necessary for hypothalamic inflammatory responses in mice, including activation of microglia.
“The presence of excess sugar in a HFD was shown to be necessary for hypothalamic inflammatory responses in mice, including the activation of microglia, the resident immune cells of the brain [58].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [58] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Interpretationreasoning§ 2. Vascular pathology and blood-brain barrier (BBB) integrity
Increased brain penetrability stands as a mechanism favoring neuroimmune activation, immune cell infiltration, and mood dysfunction.
“Obesity and cardiometabolic comorbidities impair BBB integrity [162]; thus, increased brain penetrability stands as a mechanism favoring neuroimmune activation, immune cell infiltration, and mood dysfunction.”
Quote in the paperSubstantial claim - Premisecitation§ Inflammatory conduits to the brain
Inflammation-induced depressed mood can be predicted by elevated blood mononuclear cell transcription factor activity related to immune activation (NFκB), sympathetic activation, and glucocorticoid insensitivity.
“Inflammation-induced depressed mood can be predicted by elevated blood mononuclear cell transcription factor activity related to immune activation (NFκB), sympathetic activation, and glucocorticoid (GC) insensitivity [62].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [62] source
Not checked in the free run.
- Premisecitation§ Inflammatory conduits to the brain
Individuals suffering from anxiety disorders can exhibit elevated circulating levels of inflammatory markers, including CRP, IL-1β, IL-6, and TNFα.
“Likewise, individuals suffering from anxiety disorders can exhibit elevated circulating levels of inflammatory markers, including CRP, IL-1β, IL-6, and TNFα [63]; however, the literature linking inflammation to anxiety is much sparser.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [63] source
Not checked in the free run.
- Premisecitation§ Gut dysbiosis
Human neuroimaging findings show heightened microglia activation after lipopolysaccharide administration that produces depressive-like sickness symptoms.
“Human neuroimaging findings show heightened microglia activation after LPS administration that produces depressive-like sickness symptoms [79].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [79] source
Not checked in the free run.
- Premisecitation§ 2. Vascular pathology and blood-brain barrier (BBB) integrity
Obesity and cardiometabolic comorbidities impair blood-brain barrier integrity.
“Obesity and cardiometabolic comorbidities impair BBB integrity [162]; thus, increased brain penetrability stands as a mechanism favoring neuroimmune activation, immune cell infiltration, and mood dysfunction.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [162] source
Not checked in the free run.
- Premisecitation§ Insulin
In obese individuals, decreased insulin sensitivity correlates significantly with greater depressive and anxiety symptomology.
“In obese individuals, decreased insulin sensitivity correlates significantly with greater depressive and anxiety symptomology [122,123].”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation§ 2. Vascular pathology and blood-brain barrier (BBB) integrity
Chronic stress itself can also lead to blood-brain barrier dysfunction in the nucleus accumbens to promote depressive-like behaviors in mice, changes linked to increased monocyte accumulation and reduced neuronal cAMP production.
“Interestingly, chronic stress itself can also lead to BBB dysfunction in the nucleus accumbens to promote depressive-like behaviors in mice, changes linked to increased monocyte accumulation and reduced neuronal cAMP production [167].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [167] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Interpretationreasoning§ Neuroinflammatory outcomes
Collective findings in rodents, along with reports of structural and functional changes in obese humans, support the clinical relevance of neuroinflammation in obesity-induced neuropathophysiology.
“The collective findings in rodents, along with reports of structural and functional changes in obese humans, support the clinical relevance of this mechanism.”
Quote in the paperSubstantial claim- Rests on an assumption: Findings from rodent models of diet-induced obesity and depressive/anxiety-like behaviors can be generalized to human obesity-induced depression and anxiety.
- Premisecitation§ Neuroplastic adaptations
Obesity and depression share similar morphometric anomalies in medial prefrontal cortex.
“Both obesity and depression share similar morphometric anomalies in medial prefrontal cortex [104]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [104] source
Not checked in the free run.
- Premisecitation§ Leptin
Plasma levels of the adipose-derived hormone leptin negatively correlate with symptoms of anxiety and depression in women and men.
“Plasma levels of the adipose-derived hormone leptin negatively correlate with symptoms of anxiety and depression in women and men [116].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [116] source
Not checked in the free run.
- Premisecitation§ Monoamine imbalances
Chronic HFD in male mice, leading to increased anxiety-like behavior, impairs basal electrical activity and excitability of serotonin neurons and serotonin-mediated neurotransmission in the hippocampus.
“Chronic HFD in male mice, leading to increased anxiety-like behavior, has been shown to impair the basal electrical activity and excitability of serotonin neurons as well as serotonin-mediated neurotransmission in the hippocampus [33,35].”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation§ Neuroinflammatory outcomes
Reversing neuroinflammation via targeted genetic, pharmacological, or dietary approaches that rescue behavioral anomalies supports a causal role of neuroinflammation in obesity-induced neuropathophysiology.
“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
Quote in the paperSubstantial claim0 of 6 sources checked - Premisecitation§ Monoamine imbalances
Blunted dopamine tone in the striatum has been consistently described in obese individuals and in rodent models of obesity.
“Blunted dopamine tone in the striatum has been consistently described in obese individuals and in rodent models of obesity [113].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [113] source
Not checked in the free run.
- Premisecitation§ Monoamine imbalances
Blunted serotoninergic tone has been extensively associated with mood and emotional deficits.
“blunted serotoninergic tone has been extensively associated with mood and emotional deficits [109].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [109] source
Not checked in the free run.
- Premisecitation§ Monoamine imbalances
Blunted mesolimbic dopamine signaling has been more directly implicated in anhedonia, a cardinal symptom of MDD that is ineffectively treated by SSRIs.
“Blunted mesolimbic dopamine signaling has been more directly implicated in anhedonia, a cardinal symptom of MDD that is ineffectively treated by SSRIs [114].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [114]
Not checked in the free run.
- May combine two claims. 38
- Classified as probably not a substantial claim. 4
May combine two claims.
Interpretationreasoning§ Epidemiology and clinical featuresA vicious cycle can promote disease progression because atypical depression is predictive of overeating and weight gain, and metabolic risks can be intensified by antidepressant treatments that encourage weight gain.
“As atypical depression is predictive of overeating and weight gain, and metabolic risks can be intensified by antidepressant treatments that encourage weight gain, a vicious cycle can promote disease progression.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ Epidemiology and clinical featuresThe odds and incidence of depression are higher when evaluating the waist-to-hip ratio or abdominal adiposity than when using BMI.
“The odds of depression are higher when evaluating the waist-to-hip ratio [16,17] which provides a better estimate of visceral adiposity and metabolic dysfunction than BMI [18].”
- Also stated in: § Adipose expansion · plain
“Correspondingly, depression incidence is higher when assessing abdominal adiposity or the waist-to-hip ratio as compared with BMI [17].”
Quote in the paperNot a substantial claim0 of 2 sources checked- Also stated in: § Adipose expansion · plain
May combine two claims.
Premisecitation§ Epidemiology and clinical featuresThere is a bidirectional association between being overweight (BMI ≥ 25-29.99) and depression in men and women, a relationship that is stronger for obesity (BMI ≥ 30).
“There is a bidirectional association between being overweight (BMI ≥ 25-29.99)and depression in men and women, a relationship that is stronger for obesity (BMI ≥ 30) [15].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] source
Not checked in the free run.
Probably not a substantial claim: may not pass S4 (based).
Interpretationreasoning§ Convergence of mood and metabolic deficitsNeuroinflammation alters structure, excitability, and connectivity in corticolimbic networks controlling mood, motivation, and emotion.
“Neuroinflammation alters structure, excitability, and connectivity in corticolimbic networks controlling mood, motivation, and emotion.”
Quote in the paperNot a substantial claim- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
Probably not a substantial claim: may not pass S4 (based).
Interpretationnone given§ Convergence of mood and metabolic deficitsAdipose- and gut-derived inflammation and changes in brain nutrient composition stimulate neuroinflammation.
“Adipose-and gut-derived inflammation and changes in brain nutrient composition stimulate neuroinflammation.”
Quote in the paperNot a substantial claim- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
- Rests on an assumption: Gut microbiota alterations observed in diet-induced obese mice translate to human obesity-related mood dysfunction.
May combine two claims.
Interpretationreasoning§ Convergence of mood and metabolic deficitsDiets that include excess saturated fat and sugar intake promote metabolic dysfunction, neuroinflammation, and mental health impairments.
“Diets that include excess saturated fat and sugar intake promote metabolic dysfunction, neuroinflammation, and mental health impairments.”
Quote in the paperNot a substantial claim- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
May combine two claims.
Premisecitation§ Epidemiology and clinical featuresIndividuals with atypical depression often have a more unrelenting course of depression, in part because they show a poorer response to antidepressants.
“Individuals with atypical depression often have a more unrelenting course of depression [13], in part because they show a poorer response to antidepressants [14].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [13]
Not checked in the free run.
- cites [14] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Food environment and nutrient actionsPlasma levels of arachidonic acid positively correlate with major depressive disorder severity and reduced serotonin transporter binding in the brain.
“Both EPA and DHA limit the inflammatory effect of eicosanoids derived from arachidonic acid, an omega-6 fatty acid with plasma levels that positively correlate with MDD severity and reduced serotonin transporter binding in the brain [50].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [50] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Food environment and nutrient actionsChronic saturated high-fat feeding increases saturated fatty acid levels and appreciably decreases polyunsaturated fatty acid levels in the brain of rodents.
“Moreover, chronic saturated high-fat feeding increases saturated fatty acid levels and appreciably decreases PUFA levels in the brain of rodents [49], changes that are likely one means by which saturated dietary fats generate neuroinflammatory responses and mood deficits.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [49] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
May combine two claims.
Premisecitation§ Food environment and nutrient actionsConsumption of saturated fats and plasma concentrations of palmitate positively correlate with depressive symptoms and plasma C-reactive protein in humans.
“Consumption of saturated fats [26] and plasma concentrations of the saturated fatty acid palmitate [27] positively correlate with depressive symptoms and plasma levels of the acute phase reactant C-reactive protein (CRP) in humans.”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Premisecitation§ Food environment and nutrient actionsImposed dietary n-3 deficiency in rodents diminishes brain n-3 levels and stimulates neuroinflammation and anxiety- and depressive-like behaviors.
“In contrast, low levels of blood n-3 PUFA correlate with heightened inflammatory status and depression risk in humans, whereas imposed dietary n-3 deficiency in rodents diminishes brain n-3 levels and stimulates neuroinflammation and anxiety-and depressive-like behaviors [47].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
May combine two claims.
Premisecitation§ Food environment and nutrient actionsN-3 supplementation dampens neuroinflammation and attenuates behavioral indices of mood deficits in rodents.
“Several reports link higher n-3 consumption with lower prevalence and severity of mood disturbances in humans [45] and demonstrate that n-3 supplementation dampens neuroinflammation and attenuates behavioral indices of mood deficits in rodents [46,47].”
Quote in the paperNot a substantial claim0 of 2 sources checked- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
May combine two claims.
Premisecitation§ Food environment and nutrient actionsProlonged high-fat diet elicits metabolic dysfunction and increases anxiety- and depressive-like behaviors in rodents.
“To this end, rodent research has revealed that prolonged high-fat diet (HFD) elicits metabolic dysfunction and increases anxiety-and depressive-like behaviors [28][29][30][31][32][33][34][35][36], heightens stress and hypothalamic-pituitary-adrenal (HPA) responses [37,38], and triggers neurobehavioral deficits associated with blunted mesolimbic dopamine function [39][40][41].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [28] source
Not checked in the free run.
- cites [29] source
Not checked in the free run.
- cites [30] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ Box 1. Sex, gender, and metabolic risksThe prevalence of major depressive disorder is more than threefold higher in people with type 1 diabetes than in those without, with greater rates in diabetic women than men.
“Correspondingly, the prevalence of MDD is nearly twice as high in people with type 2 diabetes [159] and more than threefold higher in people with type 1 diabetes than those without, with greater rates in diabetic women than men [160].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [160] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Food environment and nutrient actionsLow levels of blood n-3 polyunsaturated fatty acids correlate with heightened inflammatory status and depression risk in humans.
“In contrast, low levels of blood n-3 PUFA correlate with heightened inflammatory status and depression risk in humans, whereas imposed dietary n-3 deficiency in rodents diminishes brain n-3 levels and stimulates neuroinflammation and anxiety-and depressive-like behaviors [47].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Food environment and nutrient actionsOleate can improve glycemic control and plasma lipid profiles in humans and protect against inflammation, hyperphagia, and anxiodepressive behaviors in mice.
“Oleate, a monounsaturated fatty acid enriched in olive oil, can improve glycemic control and plasma lipid profiles in humans and protect against inflammation, hyperphagia, and anxiodepressive behaviors in mice [34,42].”
Quote in the paperNot a substantial claim0 of 2 sources checked- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
May combine two claims.
Premisecitation§ Gut dysbiosisDiet is the primary effector of microbiota composition, but psychological stress can also modulate flora in rodents and in patients with major depressive disorder.
“Diet is the primary effector of microbiota composition, but psychological stress can also modulate flora in rodents and in patients with MDD [69,70].”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationnone given§ Inflammatory conduits to the brainThe literature linking inflammation to anxiety is much sparser than the literature linking inflammation to depression.
“Likewise, individuals suffering from anxiety disorders can exhibit elevated circulating levels of inflammatory markers, including CRP, IL-1β, IL-6, and TNFα [63]; however, the literature linking inflammation to anxiety is much sparser.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ Gut dysbiosisBoth the obese phenotype and anxiodepressive behaviors are transmissible by transplanting gut microbiota of diet-induced obese mice to normal-weight, germ-free mice.
“Notably, both the obese phenotype [73] and anxiodepressive behaviors [74] are transmissible by transplanting gut microbiota of DIO to normal-weight, germ-free mice.”
Quote in the paperSubstantial claim0 of 2 sources checked- Rests on an assumption: Gut microbiota alterations observed in diet-induced obese mice translate to human obesity-related mood dysfunction.
May combine two claims.
Premisecitation§ Inflammatory conduits to the brainLarge cohort studies report higher CRP concentrations in depressed patients, making heightened CRP levels in obesity one of the best predictors of depression onset, particularly atypical depression.
“Notably, large cohort studies report higher CRP concentrations in depressed patients, making heightened CRP levels in obesity one of the best predictors of depression onset, particularly atypical depression [66].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [66] source
Not checked in the free run.
May combine two claims.
Premisecitation§ 2. Vascular pathology and blood-brain barrier (BBB) integrityHypertension is a leading risk factor for depression incidence in obesity and causes neurovascular changes that involve the actions of perivascular macrophages to stimulate oxidative stress and inflammation that lead to cognitive dysfunction.
“Hypertension is a leading risk factor for depression incidence in obesity and causes neurovascular changes that involve the actions of perivascular macrophages to stimulate oxidative stress and inflammation that lead to cognitive dysfunction [166].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [166] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Gut dysbiosisSeveral bacteria can produce metabolites that impact physiology and health, such as short-chain fatty acids, and molecules that affect neural signaling and excitability in mood networks, including serotonin and gamma-aminobutyric acid.
“Several bacteria can produce other metabolites that can impact physiology and health, such as short-chain fatty acids, and several molecules with that can affect neural signaling and excitability in mood networks, including serotonin and gamma-aminobutyric acid (GABA) [69].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [69] source
Not checked in the free run.
May combine two claims.
Premisecitation§ 2. Vascular pathology and blood-brain barrier (BBB) integrityThe breakdown of the blood-brain barrier produced by peripheral immune challenge (lipopolysaccharide) permits passage of bone marrow-derived immune cells into the brain, a process enhanced by diet-induced obesity and that favors depressive behaviors.
“The breakdown of the BBB produced by peripheral immune challenge (LPS) permits passage of bone marrow-derived immune cells into the brain, a process enhanced by DIO [163] and that favors depressive behaviors [164,165].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [163] source
Not checked in the free run.
- cites [164] source
Not checked in the free run.
- cites [165] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
May combine two claims.
Premisecitation§ Gut dysbiosisMicroglia dominate as contributors to neuroinflammation and several reports underscore their role in the neuroimmune pathogenesis of depression.
“Microglia dominate as contributors to neuroinflammation and several reports underscore their role in the neuroimmune pathogenesis of depression [77].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [77] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Gut dysbiosisDeletion of T cell-dependent immunoglobulin A production enhances obesity, while reducing the abundance and diversity of Clostridium.
“Deletion of T cell-dependent immunoglobulin A production enhances obesity, while reducing the abundance and diversity of Clostridium [75].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [75] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Adipose expansionIn the absence of obesity development, saturated high-fat diets can still potentiate HPA reactivity and feedback and suppress behavioral responses to rewards in rodents.
“However, in the absence of obesity development, these diets can still potentiate HPA reactivity [37] and feedback [38] and suppress behavioral responses to rewards [41].”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [37] source
Not checked in the free run.
- cites [38] source
Not checked in the free run.
- cites [41] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
May combine two claims.
Premisecitation§ Gut dysbiosisSignificant reduction of Clostridium is also observed in major depressive disorder patients and its abundance is negatively correlated to the severity of anxiety and depression.
“Interestingly, significant reduction of Clostridium is also observed in MDD patients and its abundance is negatively correlated to the severity of anxiety and depression [70].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [70] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Inflammatory conduits to the brainObese individuals exhibiting elevated inflammation, particularly increases in CRP, are more likely to meet criteria for metabolic syndrome and to develop major depressive disorder and anxiety.
“Obese individuals exhibiting elevated inflammation, particularly increases in CRP, are more likely to meet criteria for metabolic syndrome and to develop MDD and anxiety [65].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [65] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Adipose expansionExcess fat and sugar consumption favor the accumulation of visceral adipose tissue, which comprises a higher concentration of saturated fatty acids and is especially vulnerable to immune insults as compared with subcutaneous fat.
“Excess fat and sugar consumption favor the accumulation of visceral adipose tissue, which comprises a higher concentration of saturated fatty acids and is especially vulnerable to immune insults as compared with subcutaneous fat [18].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Gut dysbiosisMonocytes can infiltrate the brain and differentiate into microglia that produce an inflammatory response that contributes to anxiety-like behavior.
“In addition, monocytes can infiltrate the brain and differentiate into microglia that produce an inflammatory response that contributes to anxiety-like behavior [78].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [78] source
Not checked in the free run.
- Rests on an assumption: Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
May combine two claims.
Premisecitation§ Inflammatory conduits to the brainDietary-derived saturated fatty acids and erythrocyte content of saturated fatty acids positively correlate with circulating measures of CRP and can contribute to inflammation by favoring TLR4 signaling in macrophages.
“Dietary-derived saturated fatty acids [26] and erythrocyte content of saturated fatty acids (indicator of long-term consumption) [27], positively correlate with circulating measures of CRP and can contribute to inflammation by favoring TLR4 signaling in macrophages [67].”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
Premisecitation§ Gut dysbiosisMicrobiota from diet-induced obese mice can weaken endothelial tight junctions and trigger inflammation in both intestine and brain and promote brain insulin resistance.
“Moreover, the microbiota from DIO mice can weaken endothelial tight junctions and trigger inflammation in both intestine and brain and promote brain insulin resistance [73,74].”
Quote in the paperSubstantial claim0 of 2 sources checked- Rests on an assumption: Gut microbiota alterations observed in diet-induced obese mice translate to human obesity-related mood dysfunction.
May combine two claims.
Interpretationcitation§ Adipose expansionAbdominal adipose expansion plays a central role in the transmission of peripheral inflammation to the central nervous system because immunometabolic consequences heighten the risk of depression.
“As these immunometabolic consequences heighten the risk of depression [3], abdominal adipose expansion plays a central role in the transmission of peripheral inflammation to the CNS.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3] source
Not checked in the free run.
May combine two claims.
Interpretationreasoning§ Inflammatory conduits to the brainPeripheral immune activation figures prominently in the pathophysiology of psychiatric and metabolic disorders and is a prime instigator of depression onset in obesity.
“Peripheral immune activation figures prominently in the pathophysiology of psychiatric and metabolic disorders and resonates as a prime instigator of depression onset in obesity.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationreasoning§ Inflammatory conduits to the brainBoth diet and serum indices of inflammation associate with indices of emotional distress.
“In turn, both diet and serum indices of inflammation associate with indices of emotional distress.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ Gut dysbiosisWhile changes in microbiota composition are reported in individuals with major depressive disorder and can correlate with disease severity, the nature of microbiota alterations across studies is conflicting.
“While changes in microbiota composition are reported in individuals with MDD and can correlate with disease severity, the nature of microbiota alterations across studies are conflicting [76].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [76] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Neuroplastic adaptationsChronic HFD exposure in rodents, leading to obesity, gives rise to impairments in prefrontal cortex-dependent functions accompanied by changes in dendritic spine density and synaptic remodeling.
“chronic HFD exposure in rodents, leading to obesity, gives rise to impairments in prefrontal cortex-dependent functions that are accompanied by changes in dendritic spine density and synaptic remodeling [105].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [105] source
Not checked in the free run.
May combine two claims.
Premisecitation§ Endocrine modulators of moodHPA dysregulation contributes to weight gain in stressed individuals via the actions of cortisol to trigger palatable food intake through brain GC receptors, an effect that leads to reduced HPA activity and short-term relief of negative affective states.
“HPA dysregulation contributes to weight gain in stressed individuals via the actions of cortisol to trigger palatable food intake through brain GC receptors, an effect that leads to reduced HPA activity and short-term relief of negative affective states [119].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [119] source
Not checked in the free run.
May combine two claims.
Interpretationreasoning§ Treatment optionsDiabetes treatments could be repositioned to improve both depressive symptoms and diabetes concurrently and perhaps as an add-on strategy to improve the efficacy of other antidepressant drugs.
“These collective findings suggest that diabetes treatments could be repositioned to improve both depressive symptoms and diabetes concurrently and perhaps as an add-on strategy to improve the efficacy of other antidepressant drugs.”
Quote in the paperSubstantial claimMay combine two claims.
Premisecitation§ Monoamine imbalancesObesity-induced increases in neuroinflammation suppress serotonin signaling by increasing its clearance from the synaptic cleft in the hippocampus, providing a potential synaptic mechanism for reduced SSRI responsiveness in obese individuals with depression.
“obesity-induced increases in neuroinflammation were recently shown to suppress serotonin signaling by increasing its clearance from the synaptic cleft in the hippocampus [110], findings that provide a potential synaptic mechanism for reduced SSRI responsiveness in obese individuals with depression.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [110] source
Not checked in the free run.
May combine two claims.
Premisecitation§ LeptinLeptin resistance can elicit depressive-like behaviors in rats and is associated with atypical features of depression (increased appetite and weight) in humans.
“leptin resistance can elicit depressive-like behaviors in rats [144] and is associated with atypical features of depression (increased appetite and weight) in humans [145].”
Quote in the paperSubstantial claim0 of 2 sources checked
The paper relies on this without support.
Findings from rodent models of obesity and depressive- and anxiety-like behaviors translate to human depression and anxiety.
“Clinical observations combined with rodent models of obesity exhibiting depressive-and anxiety-like behaviors are proving valuable for uncovering the immunometabolic and neural mechanisms”
“To this end, rodent research has revealed that prolonged high-fat diet (HFD) elicits metabolic dysfunction and increases anxiety-and depressive-like behaviors [28][29][30][31][32][33][34][35][36], heightens stress and hypothalamic-pituitary-adrenal (HPA) responses [37,38], and triggers neurobehavioral deficits associated with blunted mesolimbic dopamine function [39][40][41].”
The paper relies on this without support.
Gut microbiota alterations observed in diet-induced obese mice translate to human obesity-related mood dysfunction.
“Notably, both the obese phenotype [73] and anxiodepressive behaviors [74] are transmissible by transplanting gut microbiota of DIO to normal-weight, germ-free mice.”
The paper relies on this without support.
Findings from rodent models of diet-induced obesity and depressive/anxiety-like behaviors can be generalized to human obesity-induced depression and anxiety.
“The collective findings in rodents, along with reports of structural and functional changes in obese humans, support the clinical relevance of this mechanism.”
The paper relies on this without support.
Obesity causally contributes to the development of depression and anxiety, rather than being solely a consequence or correlated.
“New research developments uncovering the metabolic and neurobiological mechanisms by which obesity heightens the risk of depression and anxiety will prove valuable for evaluating new treatment strategies”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Even if depression is known to be associated with obesity, evidences are lacking in SO.
“Even if depression is known to be associated with obesity [56,57], evidences are lacking in SO.”
From Identification of factors associated with sarcopenic obesity development: Literature review and expert panel voting (2024) · cites this paper as [57]
Cites
Physiology and neurobiology of stress and adaptation: central role of the brain
McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 4,981 · cited 1× · see citing works
“life stress presents a particular risk for the development of clinical depression or anxiety disorders in adulthood [117].”
BackgroundOverweight, Obesity, and Depression: A Systematic Review and Meta-analysis of Longitudinal Studies
Luppino, F. S., de Wit, L. M., Bouvy, P. F., Stijnen, T., Cuijpers, P., Penninx, B. W. J. H., & Zitman, F. G. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.2 · Cited by 4,322 · cited 1× · see citing works
“99) and depression in men and women, a relationship that is stronger for obesity (BMI ≥ 30) [15].”
BackgroundThe role of inflammation in depression: from evolutionary imperative to modern treatment target
Miller, A. H., & Raison, C. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2015.5 · Cited by 3,942 · see citing works
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690 · see citing works
Ross, R., Neeland, I. J., Yamashita, S., Shai, I., Seidell, J., Magni, P., Santos, R. D., Arsenault, B., Cuevas, A., Hu, F. B., et al. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0310-7 · Cited by 1,966 · cited 8× · see citing works
“This sex distinction in incidence narrows considerably in conditions of severe obesity (BMI ≥ 40) [1].”
BackgroundInfluentialChronic stress, glucocorticoid receptor resistance, inflammation, and disease risk
Cohen, S., Janicki-Deverts, D., Doyle, W. J., Miller, G. E., Frank, E., Rabin, B. S., & Turner, R. B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1118355109 · Cited by 1,419 · cited 1× · see citing works
“However, chronic stress is associated with downregulation of GC receptormediated transcriptional activity, resulting in GC insensitivity and loss of anti-inflammatory feedback [120].”
BackgroundEpidemiology of depression and diabetes: a systematic review
Roy, T., & Lloyd, C. E. (2012) · Journal of Affective Disorders · doi:10.1016/s0165-0327(12)70004-6 · Cited by 1,229 · see citing works
Depression and obesity: evidence of shared biological mechanisms
Milaneschi, Y., Simmons, W. K., van Rossum, E. F. C., & Penninx, B. W. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0017-5 · Cited by 1,073 · cited 2× · see citing works
“A meta-analytic overview illustrates that obese adults self-reporting symptoms have 23–36% increased odds of developing depressed mood as compared with nonobese controls, whereas clinically diagnosed MDD is elevated by 14–34% [2].”
BackgroundSocial stress induces neurovascular pathology promoting depression
Menard, C., Pfau, M. L., Hodes, G. E., Kana, V., Wang, V. X., Bouchard, S., Takahashi, A., Flanigan, M. E., Aleyasin, H., LeClair, K. B., et al. (2017) · Nature Neuroscience · doi:10.1038/s41593-017-0010-3 · Cited by 1,028 · see citing works
Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic
Ressler, K. J., & Mayberg, H. S. (2007) · Nature Neuroscience · doi:10.1038/nn1944 · Cited by 1,007 · cited 1× · see citing works
“As targets of deep-brain stimulation therapy, both nucleus accumbens and ventral anterior cingulate cortex stimulation are associatedwith strong antidepressant effects in treatment-resistant MDD patients [83].”
BackgroundDepression as a Microglial Disease
Yirmiya, R., Rimmerman, N., & Reshef, R. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.001 · Cited by 944 · cited 1× · see citing works
“Microglia dominate as contributors to neuroinflammation and several reports underscore their role in the neuroimmune pathogenesis of depression [77].”
BackgroundMajor depressive disorder: new clinical, neurobiological, and treatment perspectives
Kupfer, D. J., Frank, E., & Phillips, M. L. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60602-8 · Cited by 894 · cited 1× · see citing works
“Offset by common antidepressants [selective-serotonin reuptake inhibiters (SSRI)], blunted serotoninergic tone has been extensively associated with mood and emotional deficits [109].”
BackgroundStress-induced obesity and the emotional nervous system
Dallman, M. F. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2009.10.004 · Cited by 814 · cited 4× · see citing works
“Not all obese individuals have elevated cortisol and obesity development coincides with an increase in factors that enhance cortisol production, such as chronic stress, consumption of food high in sugar and fat, and reduced sleep [118,119].”
BackgroundInfluentialInflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond
Michopoulos, V., Powers, A., Gillespie, C. F., Ressler, K. J., & Jovanovic, T. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.146 · Cited by 786 · see citing works
van Sloten, T. T., Sedaghat, S., Carnethon, M. R., Launer, L. J., & Stehouwer, C. D. A. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30405-x · Cited by 702 · cited 1× · see citing works
“diometabolic comorbidities impair BBB integrity [162]; thus, increased brain penetrability stands as a mechanism favoring”
BackgroundFelger, J. C., Li, Z., Haroon, E., Woolwine, B. J., Jung, M. Y., Hu, X., & Miller, A. H. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.168 · Cited by 620 · cited 1× · see citing works
“For example, anhedonia and motor slowing are associated with increased plasma CRP and insulin resistance that correlate negatively with functional connectivity in corticolimbic reward and motor circuits [88].”
BackgroundWohleb, E. S., Powell, N. D., Godbout, J. P., & Sheridan, J. F. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1671-13.2013 · Cited by 563 · cited 1× · see citing works
“In addition, monocytes can infiltrate the brain and differentiate into microglia that produce an inflammatory response that contributes to anxiety-like behavior [78].”
BackgroundObese-type gut microbiota induce neurobehavioral changes in the absence of obesity
Bruce-Keller, A. J., Salbaum, J. M., Luo, M., Blanchard, E., Taylor, C. M., Welsh, D. A., & Berthoud, H.-R. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.07.012 · Cited by 563 · cited 3× · see citing works
“Saturated high-fat feeding and obesity can induce phylum-wide shifting in microbiota, from Bacteroidetes to Firmicutes [73], and the abundance of some Firmicutes species positively correlate with energy intake and plasma CRP levels in obese children.”
BackgroundA meta-analytic review of polyunsaturated fatty acid compositions in patients with depression
Lin, P.-Y., Huang, S.-Y., & Su, K.-P. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.03.018 · Cited by 530 · see citing works
O’Connor, J. C., André, C., Wang, Y., Lawson, M. A., Szegedi, S. S., Lestage, J., Castanon, N., Kelley, K. W., & Dantzer, R. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5032-08.2009 · Cited by 498 · cited 1× · see citing works
“The influence of inflammation on IDO shifts kynurenine metabolism towards microglial byproducts, such as 3-hydroxykynurenine and quinolinic acid, a change associated with elevated oxidative stress and glutamate excitotoxicity that could contribute to depressive symptoms [111,112].”
BackgroundInsulin resistance in brain alters dopamine turnover and causes behavioral disorders
Kleinridders, A., Cai, W., Cappellucci, L., Ghazarian, A., Collins, W. R., Vienberg, S. G., Pothos, E. N., & Kahn, C. R. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1500877112 · Cited by 486 · cited 1× · see citing works
“Deletion of insulin receptor in neurons or astrocytes was shown to promote the development of anxiety- and depressive-like symptoms [103,127].”
BackgroundKleinridders, A., Schenten, D., Könner, A. C., Belgardt, B. F., Mauer, J., Okamura, T., Wunderlich, F. T., Medzhitov, R., & Brüning, J. C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.013 · Cited by 483 · cited 1× · see citing works
“Prolonged saturated fat intake can interfere with energy homeostasis by stimulating visceral adipose deposition and inflammation in humans [23] and impairing central leptin and insulin signaling in rodents [24,25].”
BackgroundSex differences in anxiety and depression: circuits and mechanisms
Bangasser, D. A., & Cuarenta, A. (2021) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00513-0 · Cited by 479 · see citing works
Hypothalamic inflammation in obesity and metabolic disease
Jais, A., & Brüning, J. C. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88878 · Cited by 474 · cited 1× · see citing works
“Corroborating and extending findings in humans, rodent investigations illustrate the impact of high-fat and -sugar diet to stimulate reactive gliosis and upregulate cytokine and chemokine gene expression in mouse hypothalamus [89], hippocampus [90,91], nucleus accumbens [34], and ventral tegmental area [92].”
BackgroundRelationship of neurotransmitters to the symptoms of major depressive disorder.
Nutt, D. (2008) · PubMed · Cited by 470 · see citing works
Leptin: A potential novel antidepressant
Lu, X.-Y., Kim, C. S., Frazer, A., & Zhang, W. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508901103 · Cited by 446 · see citing works
Rosqvist, F., Iggman, D., Kullberg, J., Cedernaes, J., Johansson, H.-E., Larsson, A., Johansson, L., Ahlström, H., Arner, P., Dahlman, I., et al. (2014) · Diabetes · doi:10.2337/db13-1622 · Cited by 429 · cited 1× · see citing works
“Prolonged saturated fat intake can interfere with energy homeostasis by stimulating visceral adipose deposition and inflammation in humans [23] and impairing central leptin and insulin signaling in rodents [24,25].”
BackgroundSharma, S., & Fulton, S. (2013) · International Journal of Obesity · doi:10.1038/ijo.2012.48 · Cited by 424 · cited 13× · see citing works
“The effects of DIO on the hippocampus have received considerable attention because of the well-reported effects of HFD to elicit cognitive and emotional impairments [102].”
BackgroundInfluentialSelf-citationDepression and anxiety among US adults: associations with body mass index
Zhao, G., Ford, E. S., Dhingra, S., Li, C., Strine, T. W., & Mokdad, A. H. (2009) · International Journal of Obesity · doi:10.1038/ijo.2008.268 · Cited by 423 · cited 5× · see citing works
“obese men [1,157], a divergence that corresponds with lifetime prevalence independent of body weight.”
BackgroundInfluentialMannan, M., Mamun, A., Doi, S., & Clavarino, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0157240 · Cited by 421 · cited 1× · see citing works
“Emphasizing the importance of early detection and treatment, a longitudinal meta-analysis suggests that obese adolescents have a 40% increased risk of being depressed [19].”
BackgroundLayé, S., Nadjar, A., Joffre, C., & Bazinet, R. P. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014092 · Cited by 420 · cited 3× · see citing works
“In contrast, low levels of blood n-3 PUFA correlate with heightened inflammatory status and depression risk in humans, whereas imposed dietary n-3 deficiency in rodents diminishes brain n-3 levels and stimulates neuroinflammation and anxiety- and depressive-like behaviors [47].”
BackgroundGut microbiome and depression: what we know and what we need to know
Winter, G., Hart, R. A., Charlesworth, R. P. G., & Sharpley, C. F. (2018) · Reviews in the Neurosciences · doi:10.1515/revneuro-2017-0072 · Cited by 394 · cited 1× · see citing works
“While changes in microbiota composition are reported in individuals with MDD and can correlate with disease severity, the nature of microbiota alterations across studies are conflicting [76].”
BackgroundT cell-mediated regulation of the microbiota protects against obesity
Petersen, C., Bell, R., Klag, K. A., Lee, S.-H., Soto, R., Ghazaryan, A., Buhrke, K., Ekiz, H. A., Ost, K. S., Boudina, S., et al. (2019) · Science · doi:10.1126/science.aat9351 · Cited by 385 · see citing works
Gut microbiota and major depressive disorder: a systematic review and meta-analysis
Sanada, K., Nakajima, S., Kurokawa, S., Barceló-Soler, A., Ikuse, D., Hirata, A., Yoshizawa, A., Tomizawa, Y., Salas-Valero, M., Noda, Y., et al. (2020) · Journal of Affective Disorders · doi:10.1016/j.jad.2020.01.102 · Cited by 372 · cited 2× · see citing works
“Diet is the primary effector of microbiota composition, but psychological stress can alsomodulate flora in rodents and in patients withMDD [69,70].”
BackgroundSelf-citationJuruena, M. F., Bocharova, M., Agustini, B., & Young, A. H. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.09.052 · Cited by 365 · cited 1× · see citing works
“However, depression and obesity comorbidity is often defined by atypical features; this is mostly associated with normal or lower cortisol levels [121].”
BackgroundImaging robust microglial activation after lipopolysaccharide administration in humans with PET
Sandiego, C. M., Gallezot, J.-D., Pittman, B., Nabulsi, N., Lim, K., Lin, S.-F., Matuskey, D., Lee, J.-Y., O’Connor, K. C., Huang, Y., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511003112 · Cited by 356 · cited 1× · see citing works
“Human neuroimaging findings show heightened microglia activation after LPS administration that produces depressive-like sickness symptoms [79].”
BackgroundHigh-Fat Diet Induced Anxiety and Anhedonia: Impact on Brain Homeostasis and Inflammation
Dutheil, S., Ota, K. T., Wohleb, E. S., Rasmussen, K., & Duman, R. S. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.357 · Cited by 355 · see citing works
Benoit, S. C., Kemp, C. J., Elias, C. F., Abplanalp, W., Herman, J. P., Migrenne, S., Lefevre, A.-L., Cruciani-Guglielmacci, C., Magnan, C., Yu, F., et al. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36714 · Cited by 351 · cited 1× · see citing works
“Prolonged saturated fat intake can interfere with energy homeostasis by stimulating visceral adipose deposition and inflammation in humans [23] and impairing central leptin and insulin signaling in rodents [24,25].”
BackgroundFaraco, G., Sugiyama, Y., Lane, D., Garcia-Bonilla, L., Chang, H., Santisteban, M. M., Racchumi, G., Murphy, M., Van Rooijen, N., Anrather, J., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86950 · Cited by 350 · cited 1× · see citing works
“stress and inflammation that lead to cognitive dysfunction [166].”
BackgroundInduction of leptin resistance through direct interaction of C-reactive protein with leptin
Chen, K., Li, F., Li, J., Cai, H., Strom, S., Bisello, A., Kelley, D. E., Friedman-Einat, M., Skibinski, G. A., McCrory, M. A., et al. (2006) · Nature Medicine · doi:10.1038/nm1372 · Cited by 325 · cited 1× · see citing works
“Interestingly, CRP directly inhibits the binding of leptin to its receptors and blocks the ability of leptin to induce satiety and weight reduction in mice [146].”
BackgroundMinireview: Inflammation and Obesity Pathogenesis: The Hypothalamus Heats Up
Thaler, J. P., & Schwartz, M. W. (2010) · Endocrinology · doi:10.1210/en.2010-0336 · Cited by 313 · see citing works
Davis, J. F., Tracy, A. L., Schurdak, J. D., Tschöp, M. H., Lipton, J. W., Clegg, D. J., & Benoit, S. C. (2008) · Behavioral Neuroscience · doi:10.1037/a0013111 · Cited by 307 · see citing works
Chronic peripheral inflammation, hippocampal neurogenesis, and behavior
Chesnokova, V., Pechnick, R. N., & Wawrowsky, K. (2016) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2016.01.017 · Cited by 299 · cited 2× · see citing works
“High-fat feeding triggers hippocampal proinflammatory marker upregulation that can elicit depressive-like behavior, reduce neurogenesis, and impair hippocampal function [102].”
BackgroundObesity Elicits Interleukin 1-Mediated Deficits in Hippocampal Synaptic Plasticity
Erion, J., Wosiski‐Kuhn, M., Dey, A., Hao, S., Davis, C. L., Pollock, N. K., & Stranahan, A. M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.4200-13.2014 · Cited by 279 · cited 1× · see citing works
“Corroborating and extending findings in humans, rodent investigations illustrate the impact of high-fat and -sugar diet to stimulate reactive gliosis and upregulate cytokine and chemokine gene expression in mouse hypothalamus [89], hippocampus [90,91], nucleus accumbens [34], and ventral tegmental area [92].”
BackgroundDandekar, M. P., Fenoy, A. J., Carvalho, A. F., Soares, J. C., & Quevedo, J. (2018) · Molecular Psychiatry · doi:10.1038/mp.2018.2 · Cited by 264 · cited 1× · see citing works
“Recent therapeutic developments for treatment-resistant depression include the use of implanted electrodes to deliver deep-brain stimulation to the neuronal networks controlling mood and motivation for food [152].”
BackgroundObesity diminishes synaptic markers, alters microglial morphology, and impairs cognitive function
Bocarsly, M. E., Fasolino, M., Kane, G. A., LaMarca, E. A., Kirschen, G. W., Karatsoreos, I. N., McEwen, B. S., & Gould, E. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1511593112 · Cited by 250 · cited 1× · see citing works
“Both obesity and depression share similar morphometric anomalies in medial prefrontal cortex [104], and chronic HFD exposure in rodents, leading to obesity, gives rise to impairments in prefrontal cortex-dependent functions that are accompanied by changes in dendritic spine density and synaptic remodeling [105].”
BackgroundAstrocyte IKKβ/NF-κB signaling is required for diet-induced obesity and hypothalamic inflammation
Douglass, J. D., Dorfman, M. D., Fasnacht, R., Shaffer, L. D., & Thaler, J. P. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.01.010 · Cited by 248 · cited 1× · see citing works
“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
BackgroundImpaired CNS Leptin Action Is Implicated in Depression Associated with Obesity
Yamada, N., Katsuura, G., Ochi, Y., Ebihara, K., Kusakabe, T., Hosoda, K., & Nakao, K. (2011) · Endocrinology · doi:10.1210/en.2011-0004 · Cited by 247 · see citing works
Insulin signaling in the hippocampus and amygdala regulates metabolism and neurobehavior
Soto, M., Cai, W., Konishi, M., & Kahn, C. R. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1817391116 · Cited by 246 · cited 1× · see citing works
“Inhibiting insulin and IGF1 receptor signaling, specifically in the hippocampus and the amygdala, confers anxiety along with memory impairments [128].”
BackgroundGrosso, G., Micek, A., Marventano, S., Castellano, S., Mistretta, A., Pajak, A., & Galvano, F. (2016) · Journal of Affective Disorders · doi:10.1016/j.jad.2016.08.011 · Cited by 244 · cited 1× · see citing works
“Several reports link higher n-3 consumption with lower prevalence and severity of mood disturbances in humans [45] and demonstrate that n-3 supplementation dampens neuroinflammation and attenuates behavioral indices of mood deficits in rodents [46,47].”
BackgroundAndré, C., Dinel, A.-L., Ferreira, G., Layé, S., & Castanon, N. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.03.012 · Cited by 241 · see citing works
Microglial UCP2 mediates inflammation and obesity induced by high-fat feeding
Kim, J. D., Yoon, N. A., Jin, S., & Diano, S. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.08.010 · Cited by 240 · cited 1× · see citing works
“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
BackgroundInsulin induces long-term depression of ventral tegmental area dopamine neurons via endocannabinoids
Labouèbe, G., Liu, S., Dias, C., Zou, H., Wong, J. C. Y., Karunakaran, S., Clee, S. M., Phillips, A. G., Boutrel, B., & Borgland, S. L. (2013) · Nature Neuroscience · doi:10.1038/nn.3321 · Cited by 239 · see citing works
Anhedonia and the Brain Reward Circuitry in Depression
Heshmati, M., & Russo, S. J. (2015) · Current Behavioral Neuroscience Reports · doi:10.1007/s40473-015-0044-3 · Cited by 236 · cited 1× · see citing works
“Animal models of depression that reliably induce anhedonia are associated with mesolimbic dopamine abnormalities [115].”
BackgroundMilaneschi, Y., Lamers, F., Peyrot, W. J., Baune, B. T., Breen, G., Dehghan, A., Forstner, A. J., Grabe, H. J., Homuth, G., Kan, C., et al. (2017) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.3016 · Cited by 233 · cited 1× · see citing works
“Obese individuals, particularly those presenting attributes of metabolic syndrome (abdominal obesity, hyperglycemia, hypertension, elevated triglycerides), tend to develop the atypical subtype [9] (Box 1).”
BackgroundSharma, S., Fernandes, M. F., & Fulton, S. (2013) · International Journal of Obesity · doi:10.1038/ijo.2012.197 · Cited by 231 · cited 3× · see citing works
“However, in the absence of obesity development, these diets can still potentiate HPA reactivity [37] and feedback [38] and suppress behavioral responses to rewards [41].”
BackgroundLi, K., Huang, T., Zheng, J., Wu, K., & Li, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0088103 · Cited by 231 · cited 1× · see citing works
“Increased dietary n-3 intake can improve insulin sensitivity [43] and significantly diminish plasma CRP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) levels in humans [44].”
BackgroundKanoski, S. E., Meisel, R. L., Mullins, A. J., & Davidson, T. L. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2007.05.004 · Cited by 226 · see citing works
Insulin regulates astrocyte gliotransmission and modulates behavior
Cai, W., Xue, C., Sakaguchi, M., Konishi, M., Shirazian, A., Ferris, H. A., Li, M. E., Yu, R., Kleinridders, A., Pothos, E. N., et al. (2018) · Journal of Clinical Investigation · doi:10.1172/jci99366 · Cited by 222 · cited 2× · see citing works
“Deletion of insulin receptor in neurons or astrocytes was shown to promote the development of anxiety- and depressive-like symptoms [103,127].”
BackgroundHsu, T. M., Konanur, V. R., Taing, L., Usui, R., Kayser, B. D., Goran, M. I., & Kanoski, S. E. (2015) · Hippocampus · doi:10.1002/hipo.22368 · Cited by 217 · see citing works
Buckman, L. B., Hasty, A. H., Flaherty, D. K., Buckman, C. T., Thompson, M. M., Matlock, B. K., Weller, K., & Ellacott, K. L. J. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2013.06.007 · Cited by 216 · cited 9× · see citing works
“The effects of DIO on the hippocampus have received considerable attention because of the well-reported effects of HFD to elicit cognitive and emotional impairments [102].”
BackgroundInfluentialGut microbiota modulate neurobehavior through changes in brain insulin sensitivity and metabolism
Soto, M., Herzog, C., Pacheco, J. A., Fujisaka, S., Bullock, K., Clish, C. B., & Kahn, C. R. (2018) · Molecular Psychiatry · doi:10.1038/s41380-018-0086-5 · Cited by 216 · cited 2× · see citing works
“Moreover, the microbiota from DIO mice can weaken endothelial tight junctions and trigger inflammation in both intestine and brain and promote brain insulin resistance [73,74].”
BackgroundZhao, G., Ford, E. S., Li, C., Tsai, J., Dhingra, S., & Balluz, L. S. (2011) · BMC Psychiatry · doi:10.1186/1471-244x-11-130 · Cited by 214 · cited 1× · see citing works
“The odds of depression are higher when evaluating the waist-to-hip ratio [16,17] which provides a better estimate of visceral adiposity and metabolic dysfunction than BMI [18].”
Antidepressant therapies inhibit inflammation and microglial M1-polarization
Kalkman, H. O., & Feuerbach, D. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.04.001 · Cited by 212 · cited 1× · see citing works
“Consistently, suppression of microglia [80] and astrocyte [81] reactivity is implicated in the response to antidepressant therapies.”
BackgroundStress exposure, food intake and emotional state.
Ulrich‐Lai, Y. M., Fulton, S., Wilson, M., Petrovich, G. D., & Rinaman, L. (2015) · PubMed · doi:10.3109/10253890.2015.1062981 · Cited by 210 · see citing works
Self-citationMilaneschi, Y., Lamers, F., Bot, M., Drent, M. L., & Penninx, B. W. J. H. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.10.023 · Cited by 209 · cited 1× · see citing works
“In a corresponding manner, leptin resistance can elicit depressive-like behaviors in rats [144] and is associated with atypical features of depression (increased appetite and weight) in humans [145].”
BackgroundGafoor, R., Booth, H., & Gulliford, M. C. (2018) · BMJ · doi:10.1136/bmj.k1951 · Cited by 207 · cited 1× · see citing works
“Treatment options Antidepressant medications serve as the standard line of treatment; however, these drugs can be ineffective andmost augment the risk of weight gain [147].”
BackgroundInhibiting microglia expansion prevents diet-induced hypothalamic and peripheral inflammation
André, C., Guzman-Quevedo, O., Rey, C., Rémus-Borel, J., Clark, S., Castellanos-Jankiewicz, A., Ladeveze, E., Leste-Lasserre, T., Nadjar, A., Abrous, D. N., et al. (2017) · Diabetes · doi:10.2337/db16-0586 · Cited by 182 · cited 1× · see citing works
“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
BackgroundHigh-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice
Zemdegs, J., Quesseveur, G., Jarriault, D., Pénicaud, L., Fioramonti, X., & Guiard, B. P. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13343 · Cited by 180 · cited 1× · see citing works
“Chronic HFD in male mice, leading to increased anxiety-like behavior, has been shown to impair the basal electrical activity and excitability of serotonin neurons as well as serotonin-mediated neurotransmission in the hippocampus [33,35].”
BackgroundSelf-citationThe role of depressive subtypes within the neuroinflammation hypothesis of major depressive disorder
Woelfer, M., Kasties, V., Kahlfuss, S., & Walter, M. (2019) · Neuroscience · doi:10.1016/j.neuroscience.2018.03.034 · Cited by 171 · cited 2× · see citing works
“This form of depression has stronger links to peripheral [10,11] and central [12] inflammation.”
BackgroundTreatment of depression with atypical features: a meta-analytic approach
Henkel, V., Mergl, R., Allgaier, A.-K., Kohnen, R., Möller, H.-J., & Hegerl, U. (2006) · Psychiatry Research · doi:10.1016/j.psychres.2005.07.012 · Cited by 161 · cited 1× · see citing works
“Individuals with atypical depression often have a more unrelenting course of depression [13], in part because they show a poorer response to antidepressants [14].”
BackgroundSobesky, J. L., Barrientos, R. M., May, H. S. D., Thompson, B. M., Weber, M. D., Watkins, L. R., & Maier, S. F. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.06.017 · Cited by 160 · cited 1× · see citing works
“Corroborating and extending findings in humans, rodent investigations illustrate the impact of high-fat and -sugar diet to stimulate reactive gliosis and upregulate cytokine and chemokine gene expression in mouse hypothalamus [89], hippocampus [90,91], nucleus accumbens [34], and ventral tegmental area [92].”
BackgroundInsulin-mediated synaptic plasticity in the CNS: Anatomical, functional and temporal contexts
Ferrario, C. R., & Reagan, L. P. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.12.001 · Cited by 160 · cited 9× · see citing works
“The effects of DIO on the hippocampus have received considerable attention because of the well-reported effects of HFD to elicit cognitive and emotional impairments [102].”
InfluentialSchur, E. A., Melhorn, S. J., Oh, S.-K., Lacy, J. M., Berkseth, K. E., Guyenet, S. J., Sonnen, J. A., Tyagi, V., Leon, M. R. B. D., Leon, B. D., et al. (2015) · Obesity · doi:10.1002/oby.21248 · Cited by 152 · cited 1× · see citing works
“Radiologic evidence of brain gliosis that links to insulin resistance in obese adults has also been reported [87].”
BackgroundZemdegs, J., Martin, H., Pintana, H., Bullich, S., Manta, S., Marqués, M. A., Moro, C., Layé, S., Ducrocq, F., Chattipakorn, N., et al. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.2904-18.2019 · Cited by 151 · cited 2× · see citing works
“In particular, it has been proposed that peripheral insulin resistance increases branch-chained amino acids that limit the reuptake of tryptophan through the BBB, thereby limiting serotonin synthesis in the hippocampus [35].”
BackgroundSelf-citationOpel, N., Thalamuthu, A., Milaneschi, Y., Grotegerd, D., Flint, C., Leenings, R., Goltermann, J., Richter, M., Hahn, T., Woditsch, G., et al. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0774-9 · Cited by 148 · see citing works
Fish oil supplementation and insulin sensitivity: a systematic review and meta-analysis
Gao, H., Geng, T., Huang, T., & Zhao, Q. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0528-0 · Cited by 140 · cited 1× · see citing works
“Increased dietary n-3 intake can improve insulin sensitivity [43] and significantly diminish plasma CRP, interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα) levels in humans [44].”
BackgroundBrain insulin resistance: A treatment target for cognitive impairment and anhedonia in depression
Hamer, J., Testani, D. A., Mansur, R. B., Lee, Y. L., Subramaniapillai, M., & McIntyre, R. S. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.01.016 · Cited by 139 · cited 1× · see citing works
“In turn, a high percentage of patients with depression exhibit insulin resistance [124].”
BackgroundOpel, N., Redlich, R., Grotegerd, D., Dohm, K., Heindel, W., Kugel, H., Arolt, V., & Dannlowski, U. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.10.001 · Cited by 138 · cited 1× · see citing works
“Both obesity and depression share similar morphometric anomalies in medial prefrontal cortex [104], and chronic HFD exposure in rodents, leading to obesity, gives rise to impairments in prefrontal cortex-dependent functions that are accompanied by changes in dendritic spine density and synaptic remodeling [105].”
BackgroundXu, Q., Anderson, D., & Lurie-Beck, J. (2011) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2011.04.007 · Cited by 136 · cited 7× · see citing works
“This sex distinction in incidence narrows considerably in conditions of severe obesity (BMI ≥ 40) [1].”
BackgroundInfluentialMa, J., Rosas, L. G., Lv, N., Xiao, L., Snowden, M. B., Venditti, E. M., Lewis, M. A., Goldhaber-Fiebert, J. D., & Lavori, P. W. (2019) · JAMA · doi:10.1001/jama.2019.0557 · Cited by 133 · cited 1× · see citing works
“For example, adding a dietary weight loss intervention and psychotherapy has been shown to enhance the efficacy of antidepressant medications in obese individuals [148].”
BackgroundTreatment of cytokine-induced depression
Capuron, L., Hauser, P., Hinze-Selch, D., Miller, A. H., & Neveu, P. J. (2002) · Brain Behavior and Immunity · doi:10.1016/s0889-1591(02)00007-7 · Cited by 132 · cited 1× · see citing works
“observations that inflammatory interventions can lead to symptoms of these disorders, such as in the case of patients receiving interferon (IFN) alpha treatment [64].”
BackgroundHamer, M., Batty, G. D., & Kivimaki, M. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.30 · Cited by 132 · cited 1× · see citing works
“blood pressure, C-reactive protein, triglycerides, and glycaemia) present either no increased risk [161] or a modest elevated”
BackgroundJokela, M., Hamer, M., Singh-Manoux, A., Batty, G. D., & Kivimäki, M. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.162 · Cited by 132 · cited 3× · see citing works
“The odds of developing major depressive disorder (MDD) and anxiety increase as a function of the number of coexisting metabolic impairments, such as those characteristic of metabolic syndrome [3,4].”
BackgroundObesity-mediated inflammation may damage the brain circuit that regulates food intake
Cazettes, F., Cohen, J. I., Yau, P. L., Talbot, H., & Convit, A. J. (2010) · Brain Research · doi:10.1016/j.brainres.2010.12.008 · Cited by 131 · cited 1× · see citing works
“Both waist circumference [84] and circulating markers of inflammation [85] in obesity correlate negatively with cortical grey matter volume.”
BackgroundDietary sugars, not lipids, drive hypothalamic inflammation
Gao, Y., Bielohuby, M., Fleming, T., Grabner, G. F., Foppen, E., Bernhard, W., Guzmán-Ruiz, M., Layritz, C., Legutko, B., Zinser, E., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.06.008 · Cited by 131 · cited 1× · see citing works
“The presence of excess sugar in a HFD was shown to be necessary for hypothalamic inflammatory responses in mice, including the activation of microglia, the resident immune cells of the brain [58].”
BackgroundLiukkonen, T., Räsänen, P., Jokelainen, J., Leinonen, M., Järvelin, M.-R., Meyer-Rochow, V. B., & Timonen, M. (2011) · European Psychiatry · doi:10.1016/j.eurpsy.2011.02.001 · Cited by 127 · cited 1× · see citing works
“Obese individuals exhibiting elevated inflammation, particularly increases in CRP, are more likely to meet criteria for metabolic syndrome and to develop MDD and anxiety [65].”
BackgroundSpichak, S., Bastiaanssen, T. F. S., Berding, K., Vlckova, K., Clarke, G., Dinan, T. G., & Cryan, J. F. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.02.044 · Cited by 127 · cited 1× · see citing works
“Chronic changes in microbiota composition in obesity (dysbiosis) are associated with inflammation, insulin resistance, and mental health deficits [72].”
BackgroundMilos, G. F., Antel, J., Kaufmann, L., Barth, N., Koller, A., Tan, S., Wiesing, U., Hinney, A., Libuda, L., Wabitsch, M., et al. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-00977-1 · Cited by 120 · cited 1× · see citing works
“While studies in humans are limited, treatment with a leptin analog (metreleptin) has rapid antidepressant effects in individuals with anorexia nervosa marked by very low leptin levels [143].”
BackgroundHryhorczuk, C., Florea, M., Rodaros, D., Poirier, I., Daneault, C., Des Rosiers, C., Arvanitogiannis, A., Alquier, T., & Fulton, S. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.207 · Cited by 119 · cited 1× · see citing works
“However, in the absence of obesity development, these diets can still potentiate HPA reactivity [37] and feedback [38] and suppress behavioral responses to rewards [41].”
BackgroundSelf-citationDietary inflammatory index and depression: a meta-analysis
Wang, J., Zhou, Y., Chen, K., Jing, Y., He, J., Sun, H., & Hu, X. (2018) · Public Health Nutrition · doi:10.1017/s1368980018002628 · Cited by 118 · cited 1× · see citing works
“Dietary fat overload Several lines of evidence link poor diet, inflammation, and depressive symptomology [21,22].”
BackgroundTang, F., Wang, G., & Lian, Y. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.11.025 · Cited by 117 · cited 1× · see citing works
“The odds of developing major depressive disorder (MDD) and anxiety increase as a function of the number of coexisting metabolic impairments, such as those characteristic of metabolic syndrome [3,4].”
BackgroundScott, K. M., Von Korff, M., Alonso, J., Angermeyer, M., Bromet, E. J., Bruffaerts, R., de Girolamo, G., de Graaf, R., Fernandez, A., Gureje, O., et al. (2008) · Psychological Medicine · doi:10.1017/s0033291708003413 · Cited by 116 · cited 1× · see citing works
“obese men [1,157], a divergence that corresponds with lifetime prevalence independent of body weight.”
BackgroundEffects of adiposity and metabolic dysfunction on cognition: A review
Farruggia, M. C., & Small, D. M. (2019) · Physiology & Behavior · doi:10.1016/j.physbeh.2019.112578 · Cited by 112 · cited 1× · see citing works
“In this review, we focus on how obesity increases the risk for depression and anxiety (for cognitive corollaries, see [7,8]), with the aim to illuminate the diverse metabolic culprits of obesity and their influence on the neural and behavioral processes giving rise to mood and emotional deficits.”
BackgroundRole of the Brain's Reward Circuitry in Depression
Nestler, E. J. (2015) · International review of neurobiology · doi:10.1016/bs.irn.2015.07.003 · Cited by 108 · cited 3× · see citing works
“In contrast, increasing brain-derived neurotrophic factor in the nucleus accumbens or ventral tegmental area produces a depressive-like phenotype, whereas animals with selective knockout of brain-derived neurotrophic factor in ventral tegmental area are protected from depressive effects produced by social defeat stres…”
BackgroundHarrell, C. S., Burgado, J., Kelly, S. D., Johnson, Z. P., & Neigh, G. N. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.08.025 · Cited by 107 · see citing works
Décarie-Spain, L., Sharma, S., Hryhorczuk, C., Issa-Garcia, V., Barker, P. A., Arbour, N., Alquier, T., & Fulton, S. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.01.018 · Cited by 107 · cited 4× · see citing works
“Corroborating and extending findings in humans, rodent investigations illustrate the impact of high-fat and -sugar diet to stimulate reactive gliosis and upregulate cytokine and chemokine gene expression in mouse hypothalamus [89], hippocampus [90,91], nucleus accumbens [34], and ventral tegmental area [92].”
BackgroundInfluentialSelf-citationJanowitz, D., Wittfeld, K., Terock, J., Freyberger, H. J., Hegenscheid, K., Völzke, H., Habes, M., Hosten, N., Friedrich, N., Nauck, M. A., et al. (2015) · NeuroImage · doi:10.1016/j.neuroimage.2015.07.086 · Cited by 106 · cited 1× · see citing works
“Both waist circumference [84] and circulating markers of inflammation [85] in obesity correlate negatively with cortical grey matter volume.”
BackgroundWang, F., Wang, S., Zong, Q. ‐., Zhang, Q., Ng, C. H., Ungvari, G. S., & Xiang, Y. ‐. (2019) · Diabetic Medicine · doi:10.1111/dme.14042 · Cited by 105 · cited 1× · see citing works
“betes [159] and more than threefold higher in people with type 1 diabetes than those without, with greater rates in diabetic”
BackgroundKetamine’s effect on inflammation and kynurenine pathway in depression: A systematic review
Kopra, E. I., Mondelli, V., Pariante, C. M., & Nikkheslat, N. (2021) · Journal of Psychopharmacology · doi:10.1177/02698811211026426 · Cited by 102 · cited 6× · see citing works
“Adipose-derived inflammatory molecules such as TNFα disrupt insulin signaling to promote resistance and impaired vascular health.”
BackgroundInfluentialSelective deletion of leptin receptors in adult hippocampus induces depression-related behaviours
Guo, M., Huang, T.-Y., Garza, J. C., Chua, S. C., & Lu, X. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712000703 · Cited by 101 · cited 1× · see citing works
“The anxiolytic action of leptin in mice has been tied to leptin receptor signaling in mesolimbic dopamine neurons [137,138], whereas its effects to inhibit behavioral despair are attributed to signaling actions in the hippocampus [139].”
BackgroundRecognition and diagnosis of atypical depression.
Thase, M. E. (2007) · PubMed · Cited by 97 · see citing works
Role of brain transmigrating neutrophils in depression-like behavior during systemic infection
Aguliar-Valles, A., Kim, J., Jung, S., Woodside, B., & Luheshi, G. N. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.137 · Cited by 97 · cited 1× · see citing works
“DIO [163] and that favors depressive behaviors [164,165].”
BackgroundCarraça, E. V., Encantado, J., Battista, F., Beaulieu, K., Blundell, J. E., Busetto, L., van Baak, M., Dicker, D., Ermolao, A., Farpour‐Lambert, N., et al. (2021) · Obesity Reviews · doi:10.1111/obr.13261 · Cited by 97 · cited 1× · see citing works
“Although there is limited evidence for depression and obesity comorbidity, exercise has been shown to enhance mental health outcomes in obesity via ameliorating self-efficacy and autonomous motivation [156].”
BackgroundKokras, N., & Dalla, C. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.23861 · Cited by 94 · cited 2× · see citing works
“A dietary approach that includes anti-inflammatory foods and supplements, such as those containing high EPA n-3 PUFA and probiotics, could help attenuate psychological stress in obesity [149,150].”
BackgroundSivanathan, S., Thavartnam, K., Arif, S., Elegino, T., & McGowan, P. O. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.02.036 · Cited by 93 · see citing works
Kadriu, B., Farmer, C., Yuan, P., Park, L. T., Deng, Z., Moaddel, R., Henter, I. D., Shovestul, B. J., Ballard, E. D., Kraus, C., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0589-8 · Cited by 92 · cited 1× · see citing works
“The influence of inflammation on IDO shifts kynurenine metabolism towards microglial byproducts, such as 3-hydroxykynurenine and quinolinic acid, a change associated with elevated oxidative stress and glutamate excitotoxicity that could contribute to depressive symptoms [111,112].”
BackgroundHickman, R. J., Khambaty, T., & Stewart, J. C. (2014) · Journal of Behavioral Medicine · doi:10.1007/s10865-013-9510-0 · Cited by 90 · see citing works
Leptin regulates leukocyte recruitment into the brain following systemic LPS-induced inflammation
Rummel, C., Inoue, W., Poole, S., & Luheshi, G. N. (2010) · Molecular Psychiatry · doi:10.1038/mp.2009.98 · Cited by 88 · cited 1× · see citing works
“DIO [163] and that favors depressive behaviors [164,165].”
BackgroundSamara, A., Murphy, T., Strain, J. F., Rutlin, J. R., Sun, P., Neyman, O., Sreevalsan, N., Shimony, J. S., Ances, B. M., Song, S., et al. (2020) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00464 · Cited by 88 · cited 1× · see citing works
“Obese adults exhibit increased cellularity in the hippocampus and amygdala [86], whereas greater cell density in the nucleus accumbens, dorsal striatum, pallidum, hypothalamus, amygdala, and hippocampus correlates positively with waist circumference in adolescents [5].”
BackgroundNucleus accumbens cytoarchitecture predicts weight gain in children
Rapuano, K. M., Laurent, J. S., Hagler, D. J., Hatton, S. N., Thompson, W. K., Jernigan, T. L., Dale, A. M., Casey, B. J., & Watts, R. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2007918117 · Cited by 79 · cited 2× · see citing works
“Obesity is coupled to various structural and functional changes in the brain that are remarkably similar to those observed in depressive disorders, such as regionspecific increases in cell density and compromised neural connectivity and excitability [5,6].”
BackgroundObesity and cortisol: New perspectives on an old theme
van Rossum, E. F. C. (2017) · Obesity · doi:10.1002/oby.21774 · Cited by 76 · cited 2× · see citing works
“Not all obese individuals have elevated cortisol and obesity development coincides with an increase in factors that enhance cortisol production, such as chronic stress, consumption of food high in sugar and fat, and reduced sleep [118,119].”
BackgroundHypervulnerability of the adolescent prefrontal cortex to nutritional stress via reelin deficiency
Labouesse, M. A., Lassalle, O., Richetto, J., Iafrati, J., Weber‐Stadlbauer, U., Notter, T., Gschwind, T., Pujadas, L., Soriano, E., Reichelt, A. C., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.193 · Cited by 75 · cited 1× · see citing works
“Adolescence is considered a sensitive period for prefrontal cortex functional modulation by obesity, as HFD can inhibit prefrontal cortex synaptic plasticity to induce local perturbations in excitatory transmission in adolescent mice [106].”
BackgroundFinger, B. C., Dinan, T. G., & Cryan, J. F. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1858-z · Cited by 74 · see citing works
Sartorius, T., Ketterer, C., Kullmann, S., Balzer, M., Rotermund, C., Binder, S., Hallschmid, M., Machann, J., Schick, F., Somoza, V., et al. (2012) · Diabetes · doi:10.2337/db11-1521 · Cited by 73 · see citing works
Rudolf, S., Greggersen, W., Kahl, K. G., Hüppe, M., & Schweiger, U. (2014) · Psychiatry Research · doi:10.1016/j.psychres.2014.02.016 · Cited by 71 · cited 1× · see citing works
“This form of depression has stronger links to peripheral [10,11] and central [12] inflammation.”
BackgroundRole of macrophages in the endocrine system
Rehman, A., Pacher, P., & Haskó, G. (2021) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2020.12.001 · Cited by 71 · cited 1× · see citing works
“It is namely resident macrophages and T-lymphocyte immune cells that perpetuate the inflammatory situation in adipose tissue [68], and dietary saturated fatty acids can be a direct source of metabolic stress that can promote inflammation by increasing TLR4 signaling.”
BackgroundGariepy, G., Wang, J., Lesage, A. D., & Schmitz, N. (2010) · Obesity · doi:10.1038/oby.2009.333 · Cited by 70 · cited 1× · see citing works
“, dread, unease) by 30% and 40%, respectively [1,20].”
Leptin treatment ameliorates anxiety in ob/ob obese mice
Asakawa, A., Inui, A., Inui, T., Katsuura, G., Fujino, M., & Kasuga, M. (2003) · Journal of Diabetes and its Complications · doi:10.1016/s1056-8727(02)00185-x · Cited by 70 · see citing works
Insulin and ghrelin: peripheral hormones modulating memory and hippocampal function
McNay, E. C. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.10.009 · Cited by 67 · cited 1× · see citing works
“The direct effects of insulin to increase neurogenesis may also contribute to its antidepressant-like and procognitive properties [131].”
BackgroundRebelos, E., Rinne, J. O., Nuutila, P., & Ekblad, L. L. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10071532 · Cited by 66 · cited 2× · see citing works
“Reductions in glucose uptake in the hippocampus have been connected to cognitive deficits in obesity [59].”
BackgroundRole of cytokines in atypical depression
Yoon, H.-K., Kim, Y.-K., Lee, H.-J., Kwon, D.-Y., & Kim, L. (2012) · Nordic Journal of Psychiatry · doi:10.3109/08039488.2011.611894 · Cited by 65 · cited 1× · see citing works
“This form of depression has stronger links to peripheral [10,11] and central [12] inflammation.”
BackgroundLeptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors
Liu, J., Guo, M., & Lu, X. (2015) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyv115 · Cited by 65 · cited 1× · see citing works
“The anxiolytic action of leptin in mice has been tied to leptin receptor signaling in mesolimbic dopamine neurons [137,138], whereas its effects to inhibit behavioral despair are attributed to signaling actions in the hippocampus [139].”
BackgroundIncreased anxiety-like behavior is associated with the metabolic syndrome in non-stressed rats
Rebolledo-Solleiro, D., Roldán-Roldán, G., Díaz, D., Velasco, M., Larqué, C., Rico-Rosillo, G., Vega-Robledo, G. B., Zambrano, E., Hiriart, M., & Pérez de la Mora, M. (2017) · PLoS ONE · doi:10.1371/journal.pone.0176554 · Cited by 64 · see citing works
Down-regulation of cholinergic signaling in the habenula induces anhedonia-like behavior
Han, S., Yang, S. H., Kim, J. Y., Mo, S., Yang, E., Song, K. M., Ham, B., Mechawar, N., Turecki, G., Lee, H. W., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-01088-6 · Cited by 62 · cited 1× · see citing works
“Neuronal activity in the lateral habenula is associated with encoding value of cues previously paired with aversive outcomes and is posited to contribute to anhedonia [82].”
BackgroundXu, M.-X., Yu, R., Shao, L.-F., Zhang, Y.-X., Ge, C.-X., Liu, X.-M., Wu, W.-Y., Li, J.-M., & Kong, L.-D. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.01.001 · Cited by 61 · cited 1× · see citing works
“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
BackgroundEndothelium as a gatekeeper of fatty acid transport
Mehrotra, D., Wu, J., Papangeli, I., & Chun, H. J. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2013.11.001 · Cited by 60 · cited 1× · see citing works
“Brain transport of fatty acids is elevated in individuals with metabolic syndrome [48].”
BackgroundChan, R. F., Turecki, G., Shabalin, A. A., Guintivano, J., Zhao, M., Xie, L. Y., van Grootheest, G., Kaminsky, Z. A., Dean, B., Penninx, B. W. J. H., et al. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.10.014 · Cited by 60 · cited 12× · see citing works
“Correspondingly, the prevalence of MDD is nearly twice as high in people with type 2 diabetes [159] and more than threefold higher in people with type 1 diabetes than those without, with greater rates in diabetic women than men [160].”
BackgroundInfluentialUnravelling the impacts of western-style diets on brain, gut microbiota and cognition
Kendig, M. D., Leigh, S., & Morris, M. J. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.05.031 · Cited by 60 · see citing works
Auguste, S., Fisette, A., Fernandes, M. F., Hryhorczuk, C., Poitout, V., Alquier, T., & Fulton, S. (2016) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyw014 · Cited by 59 · cited 13× · see citing works
“The effects of DIO on the hippocampus have received considerable attention because of the well-reported effects of HFD to elicit cognitive and emotional impairments [102].”
BackgroundInfluentialSelf-citationGuo, M., & Lu, X.-Y. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.126 · Cited by 55 · cited 2× · see citing works
“Correspondingly, several lines of evidence point to hypodopaminergic states in MDD. Blunted mesolimbic dopamine signaling has been more directly implicated in anhedonia, a cardinal symptom of MDD that is ineffectively treated by SSRIs [114].”
BackgroundChen, G.-Q., Peng, C.-L., Lian, Y., Wang, B.-W., Chen, P.-Y., & Wang, G.-P. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.662357 · Cited by 55 · cited 1× · see citing works
“Dietary fat overload Several lines of evidence link poor diet, inflammation, and depressive symptomology [21,22].”
BackgroundLi, X., Liang, S., Li, Z., Li, S., Xia, M., Verkhratsky, A., & Li, B. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00734 · Cited by 54 · cited 2× · see citing works
“Correspondingly, several lines of evidence point to hypodopaminergic states in MDD. Blunted mesolimbic dopamine signaling has been more directly implicated in anhedonia, a cardinal symptom of MDD that is ineffectively treated by SSRIs [114].”
Transcriptomic predictors of inflammation-induced depressed mood
Cho, J. H.-J., Irwin, M. R., Eisenberger, N. I., Lamkin, D. M., & Cole, S. W. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0316-9 · Cited by 54 · see citing works
Cordeiro, R. C., Filho, A. J. M. C., Gomes, N. S., Tomaz, V. D. S., Medeiros, C. D., Queiroz, A. I. D. G., Maes, M. H. J., Macêdo, D. S., & Carvalho, A. F. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00125 · Cited by 54 · see citing works
Demers, G., Roy, J., Machuca-Parra, A. I., Dashtehei pour, Z., Bairamian, D., Daneault, C., Rosiers, C. D., Ferreira, G., Alquier, T., Fulton, S., et al. (2020) · International Journal of Obesity · doi:10.1038/s41366-020-0623-6 · Cited by 53 · cited 2× · see citing works
“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
BackgroundHypothalamic microglia as potential regulators of metabolic physiology.
Valdearcos, M., Myers, M. G., & Koliwad, S. K. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0040-0 · Cited by 52 · cited 1× · see citing works
“Microglia and astrocytes are paramount for the inflammatory pattern induced by saturated high-fat feeding and consequent metabolic impairments [93,94].”
Backgroundda Costa Estrela, D., da Silva, W. A. M., Guimarães, A. T. B., de Oliveira Mendes, B., da Silva Castro, A. L., da Silva Torres, I. L., & Malafaia, G. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.07.016 · Cited by 51 · see citing works
Liu, S., Labouèbe, G., Karunakaran, S., Clee, S. M., & Borgland, S. L. (2013) · Nutrition and Diabetes · doi:10.1038/nutd.2013.38 · Cited by 51 · cited 1× · see citing works
“In addition, insulin decreases the amplitude of excitatory currents onto ventral tegmental area dopamine neurons, effects which are blunted in DIO rats [129,130].”
BackgroundLai, J. S., Oldmeadow, C., Hure, A. J., McEvoy, M., Hiles, S. A., Boyle, M., & Attia, J. (2016) · Nutrition Research · doi:10.1016/j.nutres.2015.11.017 · Cited by 51 · cited 2× · see citing works
“Dietary-derived saturated fatty acids [26] and erythrocyte content of saturated fatty acids (indicator of long-term consumption) [27], positively correlate with circulating measures of CRP and can contribute to inflammation by favoring TLR4 signaling in macrophages [67].”
BackgroundHryhorczuk, C., Décarie-Spain, L., Sharma, S., Daneault, C., Rosiers, C. D., Alquier, T., & Fulton, S. (2017) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2017.06.002 · Cited by 51 · cited 3× · see citing works
“However, in the absence of obesity development, these diets can still potentiate HPA reactivity [37] and feedback [38] and suppress behavioral responses to rewards [41].”
BackgroundNakajima, S., Fukasawa, K., Gotoh, M., Murakami‐Murofushi, K., & Kunugi, H. (2019) · International Journal of Obesity · doi:10.1038/s41366-019-0468-z · Cited by 50 · see citing works
Self-citationDepressive symptoms, anxiety and well-being among metabolic health obese subtypes
Phillips, C. M., & Perry, I. J. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.07.168 · Cited by 48 · see citing works
Martin, H., Bullich, S., Guiard, B. P., & Fioramonti, X. (2021) · Journal of Neuroendocrinology · doi:10.1111/jne.12928 · Cited by 48 · cited 3× · see citing works
“Diabetes medications exhibit promising antidepressant and anxiolytic actions [125].”
BackgroundInfluentialSelf-citationHersey, M., Woodruff, J. L., Maxwell, N., Sadek, A. T., Bykalo, M. K., Bain, I., Grillo, C. A., Piroli, G. G., Hashemi, P., & Reagan, L. P. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.05.010 · Cited by 48 · cited 1× · see citing works
“Similarly, obesity-induced increases in neuroinflammation were recently shown to suppress serotonin signaling by increasing its clearance from the synaptic cleft in the hippocampus [110], findings that provide a potential synaptic mechanism for reduced SSRI responsiveness in obese individuals with depression.”
BackgroundRecent Advances in the Cellular and Molecular Mechanisms of Hypothalamic Neuronal Glucose Detection
Fioramonti, X., Chrétien, C., Leloup, C., & Pénicaud, L. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00875 · Cited by 44 · cited 1× · see citing works
“It is well known that glucose can also alter the electrical activity of specialized neuronal populations in the hypothalamus [60]; whether these glucose-sensing neurons are involved in the control of mood remains to be elucidated.”
BackgroundSelf-citationTsuboi, H., Watanabe, M., Kobayashi, F., Kimura, K., & Kinae, N. (2013) · Clinical Nutrition · doi:10.1016/j.clnu.2012.07.011 · Cited by 42 · cited 2× · see citing works
“Dietary-derived saturated fatty acids [26] and erythrocyte content of saturated fatty acids (indicator of long-term consumption) [27], positively correlate with circulating measures of CRP and can contribute to inflammation by favoring TLR4 signaling in macrophages [67].”
BackgroundPerry, B. I., Khandaker, G. M., Marwaha, S., Thompson, A., Zammit, S., Singh, S. P., & Upthegrove, R. (2020) · Psychological Medicine · doi:10.1017/s0033291719000308 · Cited by 42 · cited 1× · see citing works
“Insulin In obese individuals, decreased insulin sensitivity correlates significantly with greater depressive and anxiety symptomology [122,123].”
BackgroundUl-Haq, Z., Smith, D. J., Nicholl, B. I., Cullen, B., Martin, D., Gill, J. M., Evans, J., Roberts, B., Deary, I. J., Gallacher, J., et al. (2014) · BMC Psychiatry · doi:10.1186/1471-244x-14-153 · Cited by 41 · see citing works
Dopamine signalling adaptations by prolonged high-fat feeding
Décarie-Spain, L., Hryhorczuk, C., & Fulton, S. (2016) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2016.03.010 · Cited by 39 · cited 1× · see citing works
“Blunted dopamine tone in the striatum has been consistently described in obese individuals and in rodent models of obesity [113].”
BackgroundSelf-citationMassive weight loss following deep brain stimulation of the nucleus accumbens in a depressed woman
Tronnier, V. M., Rasche, D., Thorns, V., Alvarez‐Fischer, D., Münte, T. F., & Zurowski, B. (2018) · Neurocase · doi:10.1080/13554794.2018.1431678 · Cited by 37 · see citing works
Production of psychoactive metabolites by gut bacteria
Wiley, N. C., Cryan, J. F., Dinan, T. G., Ross, R. P., & Stanton, C. (2021) · Modern trends in psychiatry · doi:10.1159/000510419 · Cited by 37 · cited 2× · see citing works
“Diet is the primary effector of microbiota composition, but psychological stress can alsomodulate flora in rodents and in patients withMDD [69,70].”
BackgroundRestivo, M. R., McKinnon, M. C., Frey, B. N., Hall, G. B., Syed, W., & Taylor, V. H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0176898 · Cited by 36 · cited 1× · see citing works
“Obese individuals and animal models of obesity present poorer performance on diverse cognitive tasks and these deficits are exacerbated in instances of comorbid depressive disorder [155].”
BackgroundOf 'junk food' and 'brain food': how parental diet influences offspring neurobiology and behaviour
Bodden, C., Hannan, A. J., & Reichelt, A. C. (2021) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2021.04.001 · Cited by 36 · cited 1× · see citing works
“In addition, mounting evidence suggests that microbiota alterations mediate diet-induced parental programming of offspring neurobehavioral function and mood disorder susceptibility [71].”
BackgroundGutiérrez‐Martos, M., Girard, B., Mendonça‐Netto, S., Perroy, J., Valjent, E., Maldonado, R., & Martin, M. (2018) · Addiction Biology · doi:10.1111/adb.12541 · Cited by 35 · cited 1× · see citing works
“Reversing neuroinflammation via targeted genetic [96,97], pharmacological [98,99], or dietary [49,100] approaches that rescue behavioral anomalies offers convincing support for a causal role of neuroinflammation in obesity-induced neuropathophysiology.”
BackgroundEndocrine factors in key structural and intracellular changes in depression
Gold, P. W. (2021) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2021.01.003 · Cited by 35 · cited 2× · see citing works
“Leptin Plasma levels of the adipose-derived hormone leptin negatively correlate with symptoms of anxiety and depression in women and men [116].”
BackgroundSoriguer, F., Rojo-Martínez, G., Goday, A., Bosch-Comas, A., Bordiú, E., Caballero-Díaz, F., Calle-Pascual, A., Carmena, R., Casamitjana, R., Castaño, L., et al. (2013) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2013.130 · Cited by 34 · cited 1× · see citing works
“Oleate, a monounsaturated fatty acid enriched in olive oil, can improve glycemic control and plasma lipid profiles in humans and protect against inflammation, hyperphagia, and anxiodepressive behaviors in mice [34,42].”
BackgroundHypothalamic Astrocytes as a Specialized and Responsive Cell Population in Obesity
González‐García, I., & García‐Cáceres, C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126176 · Cited by 34 · cited 1× · see citing works
“Microglia and astrocytes are paramount for the inflammatory pattern induced by saturated high-fat feeding and consequent metabolic impairments [93,94].”
BackgroundXu, T. J., & Reichelt, A. C. (2018) · Neuropharmacology · doi:10.1016/j.neuropharm.2018.04.012 · Cited by 33 · see citing works
Anxiety-like behavior in female mice is modulated by STAT3 signaling in midbrain dopamine neurons
Fernandes, M. F., Lau, D., Sharma, S., & Fulton, S. E. (2021) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2021.04.013 · Cited by 28 · cited 1× · see citing works
“The anxiolytic action of leptin in mice has been tied to leptin receptor signaling in mesolimbic dopamine neurons [137,138], whereas its effects to inhibit behavioral despair are attributed to signaling actions in the hippocampus [139].”
BackgroundSelf-citationCarrier, N., Wang, X., Sun, L., & Lu, X. (2015) · Endocrinology · doi:10.1210/en.2015-1029 · Cited by 26 · cited 1× · see citing works
“In a consistent manner, leptin can suppress anxiety-like behavior [132–135] and behavioral despair [136] in mice.”
BackgroundAstrocytic TNFα regulates the behavioral response to antidepressants
Duseja, R., Heir, R., Lewitus, G. M., Altimimi, H. F., & Stellwagen, D. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.09.012 · Cited by 25 · cited 1× · see citing works
“Consistently, suppression of microglia [80] and astrocyte [81] reactivity is implicated in the response to antidepressant therapies.”
BackgroundZemdegs, J., Rainer, Q., Grossmann, C. P., Rousseau-Ralliard, D., Grynberg, A., Ribeiro, E., & Guiard, B. P. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00974 · Cited by 23 · cited 1× · see citing works
“Several reports link higher n-3 consumption with lower prevalence and severity of mood disturbances in humans [45] and demonstrate that n-3 supplementation dampens neuroinflammation and attenuates behavioral indices of mood deficits in rodents [46,47].”
BackgroundSelf-citationZeng, B., Zeng, B., Chen, Y., Hung, C., Sun, C., Cheng, Y., Stubbs, B., Carvalho, A. F., Brunoni, A. R., Su, K., et al. (2021) · International Journal of Obesity · doi:10.1038/s41366-021-00833-2 · Cited by 19 · cited 1× · see citing works
“For example, deep-brain stimulation in the nucleus accumbens has been shown to be effective at reducing body weight in obese rodents and patients [153] and may offer superior weight-reducing and antidepressant effects when combined with bariatric surgery [154].”
BackgroundLeptin resistance elicits depressive-like behaviors in rats
Macht, V. A., Vazquez, M., Petyak, C. E., Grillo, C. A., Kaigler, K., Enos, R. T., McClellan, J. L., Cranford, T. L., Murphy, E. A., Nyland, J. F., et al. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.10.008 · Cited by 16 · cited 1× · see citing works
“In a corresponding manner, leptin resistance can elicit depressive-like behaviors in rats [144] and is associated with atypical features of depression (increased appetite and weight) in humans [145].”
BackgroundMizoguchi, A., Banno, R., Sun, R., Yaginuma, H., Taki, K., Kobayashi, T., Sugiyama, M., Tsunekawa, T., Onoue, T., Takagi, H., et al. (2021) · Scientific Reports · doi:10.1038/s41598-021-92386-7 · Cited by 16 · cited 1× · see citing works
“Corroborating and extending findings in humans, rodent investigations illustrate the impact of high-fat and -sugar diet to stimulate reactive gliosis and upregulate cytokine and chemokine gene expression in mouse hypothalamus [89], hippocampus [90,91], nucleus accumbens [34], and ventral tegmental area [92].”
BackgroundO’Flaherty, B., Neigh, G. N., & Rainnie, D. (2019) · Behavioural Brain Research · doi:10.1016/j.bbr.2019.02.042 · Cited by 12 · see citing works
Flagged first, then by citations
6 of the 173 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Kunugi, H. (2023) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.13551 · Cited by 112 · see citing works
“In addition to inflammation, insulin resistance and leptin resistance are supposed to be involved in the pathophysiology of the bidirectional relationship between depression and excessive energy intake.(196) A molecular basis underlying the antidepressant actions of calorie restriction might involve orexin signaling a…”
BackgroundNeural interfaces: Bridging the brain to the world beyond healthcare
Xu, S., Liu, Y., Lee, H., & Li, W. (2024) · Exploration · doi:10.1002/exp.20230146 · Cited by 96 · see citing works
Tobaiqy, M. A., & Elkout, H. (2024) · International Journal of Clinical Pharmacy · doi:10.1007/s11096-023-01694-7 · Cited by 119 · see citing works
“Although obesity may increase the risk of psychiatric disorders, mental health conditions also contribute to the development or worsening of obesity through various mechanisms such as emotional eating and decreased motivation for physical activity [34, 35].”
BackgroundObesity: pathophysiology and therapeutic interventions
Kong, Y., Yang, H., Nie, R., Zhang, X., Zuo, F., Zhang, H., & Nian, X. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00264-9 · Cited by 89 · see citing works
GLP-1 agonists for weight loss: pharmacology and clinical implications.
Moore, P. W., Malone, K., VanValkenburg, D., Rando, L. L., Williams, B. C., Matejowsky, H. G., Ahmadzadeh, S., Shekoohi, S., Cornett, E. M., & Kaye, A. D. (2023) · Advances in Therapy · doi:10.1007/s12325-022-02394-w · Cited by 86 · see citing works
“Regarding the mental consequences of obesity, poor diet and lack of exercise, chronic inflammation, and insulin and leptin resistance have been identified as key risk factors for developing depression and anxiety [6].”
BackgroundBizzozero‐Peroni, B., Martínez‐Vizcaíno, V., Fernández‐Rodríguez, R., Jiménez‐López, E., de Arenas‐Arroyo, S. N., Saz‐Lara, A., Goñi, V. D., & Mesas, A. E. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuad176 · Cited by 84 · see citing works
Shared biological mechanisms of depression and obesity: focus on adipokines and lipokines
Fu, X., Wang, Y., Zhao, F., Cui, R., Xie, W., Liu, Q., & Yang, W. (2023) · Aging · doi:10.18632/aging.204847 · Cited by 76 · see citing works
The impact of obesity: a narrative review
Lam, B. C. C., Lim, A. Y. L., Chan, S. L., Yum, M. P. S., Koh, N. S. Y., & Finkelstein, E. A. (2023) · Singapore Medical Journal · doi:10.4103/singaporemedj.smj-2022-232 · Cited by 74 · see citing works
“either directly or indirectly impact the control of emotions and mood.[73,74] Hence, the causal relationship between obesity and”
Backgroundde Paiva, I. H. R., Maciel, L. M., da Silva, R. S., Mendonça, I. P., de Souza, J. D., & Peixoto, C. A. (2024) · Food Research International · doi:10.1016/j.foodres.2024.114153 · Cited by 70 · see citing works
Zhang, Q., Jin, K., Chen, B., Liu, R., Cheng, S., Zhang, Y., & Lü, J. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.884579 · Cited by 60 · see citing works
“The resulting metabolic and inflammatory dysfunction of obesity played a role in developing depression with an impact on the neuroimmune status and neural circuits controlling mood and emotional states (Fulton et al., 2022).”
BackgroundDoes intermittent fasting impact mental disorders? A systematic review with meta-analysis
Fernández‐Rodríguez, R., Martínez‐Vizcaíno, V., Mesas, A. E., Notario‐Pacheco, B., Medrano, M., & Heilbronn, L. K. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2088687 · Cited by 59 · see citing works
“In this sense, prevalence of obesity is also rapidly increasing (Grannell et al. 2021) with a bidirectional relationship between mental disorders and metabolic dysfunction caused by excess adiposity (Fulton et al. 2022).”
BackgroundKokka, I., Mourikis, I., & Bacopoulou, F. (2023) · Children · doi:10.3390/children10020285 · Cited by 53 · see citing works
“In addition, manifestations of these disorders at a cognitive and behavioral level may complicate and obstruct compliance to health management interventions, such as weight regulation [73].”
Backgroundde Wit, L. M., ten Have, M., Cuijpers, P. J., & de Graaf, R. (2022) · BMC Psychiatry · doi:10.1186/s12888-022-04077-w · Cited by 50 · see citing works
“Both psychological as well as biological factors seem to have an influence on the association [15, 16, 18, 19].”
BackgroundHigh-fat diet and neuroinflammation: The role of mitochondria
Song, M., Bai, Y., & Song, F. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107615 · Cited by 54 · see citing works
Pharmacologic Treatment of Obesity in Reproductive Aged Women
Nuako, A. A., Tu, L., Reyes, K. J. C., Chhabria, S. M., & Stanford, F. C. (2023) · Current Obstetrics and Gynecology Reports · doi:10.1007/s13669-023-00350-1 · Cited by 55 · see citing works
Lin, M.-H., Cheng, P.-C., Hsiao, P.-J., Chen, S.-C., Hung, C.-H., Kuo, C.-H., Huang, S.-K., & Clair Chiou, H.-Y. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2022.109653 · Cited by 42 · see citing works
Depression and obesity: Focus on factors and mechanistic links
Selman, A., Dai, J., Driskill, J., Reddy, A. P., & Reddy, P. H. (2024) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2024.167561 · Cited by 46 · see citing works
Wang, Z., Cheng, Y., Li, Y., Han, J., Yuan, Z., Li, Q., Zhong, F., Wu, Y., Fan, X., Bo, T., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.880230 · Cited by 40 · see citing works
“org 5 contribute to the occurrence and development of depression (13).”
BackgroundIt’s not the thought that counts: Allostasis at the core of brain function
Theriault, J. E., Katsumi, Y., Reimann, H. M., Zhang, J., Deming, P., Dickerson, B. C., Quigley, K. S., & Barrett, L. F. (2025) · Neuron · doi:10.1016/j.neuron.2025.09.028 · Cited by 49 · see citing works
Comorbidity of Anxiety and Hypertension: Common Risk Factors and Potential Mechanisms
Qiu, T., Jiang, Z., Chen, X., Dai, Y., & Zhao, H. (2023) · International Journal of Hypertension · doi:10.1155/2023/9619388 · Cited by 40 · see citing works
GDF15 links adipose tissue lipolysis with anxiety
Townsend, L. K., Wang, D., Knuth, C. M., Fayyazi, R., Mohammad, A., Becker, L. J., Tsakiridis, E. E., Desjardins, E. M., Patel, Z., Valvano, C. M., et al. (2025) · Nature Metabolism · doi:10.1038/s42255-025-01264-3 · Cited by 40 · see citing works
“48).”
Valentin‐Escalera, J., Leclerc, M., & Calon, F. (2024) · Journal of Alzheimer s Disease · doi:10.3233/jad-230118 · Cited by 35 · see citing works
The global prevalence of overweight and obesity among nurses: A systematic review and meta‐analyses
Sadali, U. B., Kamal, K. K. B. N., Park, J., Chew, H. S. J., & Devi, M. K. (2023) · Journal of Clinical Nursing · doi:10.1111/jocn.16861 · Cited by 36 · see citing works
Lama, A., Piano, F. D., Annunziata, C., Comella, F., Opallo, N., Melini, S., Grumetto, L., Pirozzi, C., Raso, G. M., Meli, R., et al. (2022) · Life Sciences · doi:10.1016/j.lfs.2022.121301 · Cited by 29 · see citing works
Mindful eating for weight loss in women with obesity: a randomised controlled trial
Pepe, R. B., Coelho, G. S. D. M. A., Miguel, F. D. S., Gualassi, A. C., Sarvas, M. M., Cercato, C., Mancini, M. C., & de Melo, M. E. (2022) · British Journal Of Nutrition · doi:10.1017/s0007114522003932 · Cited by 30 · see citing works
“Mental health is also a concern in individuals with obesity, with studies reporting high rates of depression(3,4), stress(5) and anxiety(6) among this population.”
BackgroundGe, Z., Hu, Y., Kan, W., Li, L., Xu, J., Zhang, Y., Zheng, N., Wang, G., & Du, J. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1625087 · Cited by 33 · see citing works
McCall, K. L., Mastro, K. A., Casey, R. T., Samana, T. N., Sulicz, E. K., Tso, S. Y., Yalanzhi, E. R., & Piper, B. J. (2025) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2025.2499670 · Cited by 28 · see citing works
“Depression itself is associated with chronic diseases such as diabetes and obesity [24,25].”
Qi, R., Sheng, B., Zhou, L., Chen, Y., Sun, L., & Zhang, X. (2023) · Nutrients · doi:10.3390/nu15122721 · Cited by 29 · see citing works
The enigma of vascular depression in old age: a critical update
Jellinger, K. A. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-022-02521-5 · Cited by 27 · see citing works
Gallagher, C., Pirkis, J., Lambert, K. A., Perret, J. L., Ali, G. B., Lodge, C., Bowatte, G., Hamilton, G. S., Matheson, M. C., Bui, D., et al. (2023) · International Journal of Obesity · doi:10.1038/s41366-023-01312-6 · Cited by 26 · see citing works
“as a key catalyst for depression, and possibly anxiety, by triggering dysregulation of the hypothalamic-pituitary-adrenal axis, with activated immune-inflammatory pathways inducing neuroendocrine abnormalities [24].”
BackgroundFan, Y., Zhao, L., Deng, Z., Li, M., Huang, Z., Zhu, M., & Xu, W. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.936283 · Cited by 25 · see citing works
“The prevalence of depression is known to be increased in the setting of obesity, a condition that promotes inflammation as well as resistance to insulin and leptin (43, 44).”
BackgroundGains and Losses: Resilience to Social Defeat Stress in Adolescent Female Mice
Pantoja-Urbán, A. H., Richer, S., Mittermaier, A., Giroux, M., Nouel, D., Hernández, G., & Flores, C. (2023) · Biological Psychiatry · doi:10.1016/j.biopsych.2023.06.014 · Cited by 25 · see citing works
Pinel, A., Guillet, C., Capel, F., Pouget, M., De Antonio, M., Pereira, B., Topinkova, E., Eglseer, D., Barazzoni, R., Cruz-Jentoft, A. J., et al. (2024) · Clinical Nutrition · doi:10.1016/j.clnu.2024.04.033 · Cited by 24 · see citing works
Zhao, D., Chen, Y., Xia, J., Li, Z., Kang, Y., Xiao, Z., & Niu, Y. (2024) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2024.104602 · Cited by 25 · see citing works
Zheng, Y., Yin, K., Li, L., Wang, X., Li, H., Li, W., & Fang, Z. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.06.103 · Cited by 24 · see citing works
Glucose metabolism impairment in major depressive disorder
Meng, F., Wang, J., Wang, L., & Zou, W. (2025) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2025.111191 · Cited by 23 · see citing works
Zhang, W., Nan, N., He, Y., Zuo, H., Song, X., Zhang, M., & Zhou, Y. (2022) · Psychology Health & Medicine · doi:10.1080/13548506.2022.2104885 · Cited by 23 · see citing works
“The link between obesity and depression and anxiety has also been proved by some studies (Fulton et al., 2022; Wang et al., 2019).”
ResultZhang, S., Lin, T., Zhang, Y., Liu, X., & Huang, H. (2022) · PLoS ONE · doi:10.1371/journal.pone.0276469 · Cited by 26 · see citing works
Yu, H., Yu, B., Qin, X., & Shan, W. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.07.005 · Cited by 25 · see citing works
Nakajima, S., Demers, G., Machuca‐Parra, A. I., Pour, Z. D., Bairamian, D., Bouyakdan, K., Fisette, A., Kabahizi, A., Robb, J. L., Rodaros, D., et al. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02978-5 · Cited by 25 · see citing works
“…and if GPR120 stimulation protects against the activation of NAc microglia in response to central of TNF-α and IL-1β—two cytokines required for the innate immune response, that influence affective states and that are upregulated in the brain in response to systemic LPS, stress and obesity [2, 29].”
BackgroundSelf-citationMiao, C., Wang, L., Wang, H., et al. (2024) · Food & Function · doi:10.1039/d4fo03591g · Cited by 23 · see citing works
Kaner, G., Depboylu, G. Y., Çalık, G., Yalçın, T., & Nalçakan, T. (2022) · Public Health Nutrition · doi:10.1017/s1368980022002579 · Cited by 24 · see citing works
“Studies have shown that depression, stress and anxiety are higher in obese participants (33 – 35) .”
BackgroundFemale obesity: clinical and psychological assessment toward the best treatment
Guglielmi, V., Grave, R. D., Leonetti, F., & Solini, A. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1349794 · Cited by 29 · see citing works
Body composition, lifestyle, and depression: a prospective study in the UK biobank
Lv, X., Cai, J., Li, X., Wang, X., Ma, H., Heianza, Y., Qi, L., & Zhou, T. (2024) · BMC Public Health · doi:10.1186/s12889-024-17891-6 · Cited by 23 · see citing works
“…the risk of depression than those who lead an unfavorable lifestyle [15, 16, 25, 48, 49], and the adverse lifestyles could be a risk factor for adverse body composition and may share similar pathways with adverse body composition, such as metabolic dysfunction, that contribute to depression [50].”
BackgroundWang, X., Liang, X., Jiang, M., Wei, L., Shi, X., Fang, F., & Cang, J. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-06892-3 · Cited by 25 · see citing works
“Psychosocial factors such as body image dissatisfaction, diminished self-esteem, and social stigma may contribute to the increased risk of depression in individuals with obesity [18, 19].”
Hamasaki, H. (2023) · Medicines · doi:10.3390/medicines10090053 · Cited by 26 · see citing works
“Mindfulness could be a feasible and supportive practice for people with diabetes who also suffer from stress, depression, and anxiety; however, more rigorous scientific evidence will be needed in the future.”
BackgroundLi, D., Liang, W., Zhang, W., Huang, Z., Liang, H., & Liu, Q. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1241309 · Cited by 21 · see citing works
Lv, Y., Peng, X., Lee, Y., et al. (2024) · Food Research International · doi:10.1016/j.foodres.2024.114900 · Cited by 20 · see citing works
Chang, Z., Zhu, Y., Wang, P., Du, L., Wu, M., Wang, X., Kong, C., Huang, D., Xie, R., Guo, J., et al. (2025) · 中国科学通报：英文版 · doi:10.1016/j.scib.2025.04.010 · Cited by 20 · see citing works
Magdy, Y., Kamar, S. A., Habib, M. Z., Rady, H. Y., Rabei, M. R., & Khedr, S. A. (2025) · Psychopharmacology · doi:10.1007/s00213-025-06834-7 · Cited by 20 · see citing works
“It is no wonder that the incidence of both conditions has increased steadily over the past few years (Fulton et al. 2022 ).”
Huang, J., Li, R.-H., & Tsai, L. (2022) · Nutrients · doi:10.3390/nu14194200 · Cited by 20 · see citing works
“Growing evidence suggests that obesity may increase the risk of depression [14,42].”
Backgroundde Ceglia, M., Bonaventura, M. V. M. D., Romano, A., Friuli, M., Bonaventura, E. M. D., Gavito, A., Botticelli, L., Gaetani, S., de Fonseca, F. R., & Cifani, C. (2023) · International Journal of Eating Disorders · doi:10.1002/eat.23917 · Cited by 21 · see citing works
Liu, S., Jiang, W., Liu, C., Guo, S., Wang, H., & Chang, X. (2023) · Food & Function · doi:10.1039/d3fo00604b · Cited by 20 · see citing works
Prevalence and Determinants of Depression, Anxiety, and Stress Among Secondary School Students
Barnawi, M. M., Sonbaa, A. M., Barnawi, M. M., Alqahtani, A. H., & Fairaq, B. A. (2023) · Cureus · doi:10.7759/cureus.44182 · Cited by 20 · see citing works
Landgraaf, R. G., Bloem, M. N., Fumagalli, M., Benninga, M. A., de Lorijn, F., & Nieuwdorp, M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1236370 · Cited by 21 · see citing works
“Additionally, there is a bidirectional link between anxiety, depression, and obesity (88, 89).”
Obesity and Depression: A Pathophysiotoxic Relationship
Monsalve, F. A., Fernández-Tapia, B., Arriagada, O., González, D. R., & Delgado‐López, F. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262311590 · Cited by 22 · see citing works
“…is complex, as not all obese individuals have elevated cortisol levels, and the development of obesity coincides with an increase in factors that enhance cortisol production, such as chronic stress, chronic low-grade inflammation, consumption of sugar-and fat-rich foods, and reduced sleep [51].”
InfluentialGallagher, C., Waidyatillake, N. T., Pirkis, J., Lambert, K. A., Cassim, R., Dharmage, S. C., & Erbas, B. (2023) · Obesity Reviews · doi:10.1111/obr.13566 · Cited by 18 · see citing works
“Within this growing evidence base, obesity has garnered much attention, with mental disorders thought to be a possible consequence of weight-related stigma and discrimination,(2) low selfesteem,(3) functional impairment,(3) and metabolic disturbance.(4) Indeed, several systematic reviews and meta-analyses of longitudi…”
BackgroundCustodio, R. J. P., Hobloss, Z., Myllys, M., Hassan, R. A. R. A., González, D., Reinders, J., Bornhorst, J., Weishaupt, A.-K., Seddek, A., Abbas, T., et al. (2023) · Cells · doi:10.3390/cells12182331 · Cited by 19 · see citing works
Obesogenic diet induces circuit-specific memory deficits in mice
Bakoyiannis, I., Ducourneau, E., N’diaye, M., Fermigier, A., Ducroix-Crepy, C., Bosch‐Bouju, C., Coutureau, É., Trifilieff, P., & Ferreira, G. (2024) · eLife · doi:10.7554/elife.80388 · Cited by 17 · see citing works
Liu, H., Dong, H., Zhou, Y., Jin, M., Hao, H., Yuan, Y., & Jia, H. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1482003 · Cited by 18 · see citing works
“When it comes to depression in women, those who are obese are more likely to experience it than those who are not (1, 9).”
BackgroundLin, Y., Cheng, S., Liu, W., Zailani, H., Wu, S., Hung, M., & Su, K. (2024) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2024.10.028 · Cited by 18 · see citing works
Han, X., Zhang, H., Xu, T., Liu, L. L., Cai, H., Liu, Z., Li, Q., Zheng, H., Xu, T., & Yuan, T. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.873953 · Cited by 17 · see citing works
“Especially when anxiety and depression themselves are highly correlated with obesity (49), it is a very dangerous move to try to eliminate the major factors, which may be the abnormal phenotypes shared by anxiety and depression with obesity.”
BackgroundRelationship of perceived depression, stress, anxiety levels and hedonic hunger
Yalçın, T., Ayyıldız, F., Yılmaz, M. V., & Asil, E. (2023) · International Journal of Obesity · doi:10.1038/s41366-023-01315-3 · Cited by 18 · see citing works
“Studies have shown that depression, stress and anxiety are higher in people with obesity [42, 43].”
BackgroundAalipanah, E., Askarpour, M., Eskandari, M. H., Zare, M., Famouri, M., Bedeltavana, A., Mohsenpour, M. A., & Sohrabi, Z. (2025) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2025.05.045 · Cited by 19 · see citing works
Zhang, C., Ma, W., Chen, Z., He, C., Zhang, Y., & Tao, Q. (2022) · Nutrients · doi:10.3390/nu14214508 · Cited by 21 · see citing works
“Obese adults have increased odds of depressive and anxiety symptoms compared with non-obese people [56,57].”
BackgroundPotential Benefits of Anthocyanins in Chronic Disorders of the Central Nervous System
Panchal, S. K., & Brown, L. (2022) · Molecules · doi:10.3390/molecules28010080 · Cited by 17 · see citing works
“Obesity defined as an increased body mass index predicts chronic anxiety and depression symptoms likely related to prolonged inflammation due to poor dietary lifestyle and inactivity [80].”
BackgroundWu, S., Chen, W.-J., Chang, J. P., Guu, T., Hsin, M.-C., Huang, C., Mischoulon, D., Capuron, L., & Su, K. (2023) · Journal of Personalized Medicine · doi:10.3390/jpm13061003 · Cited by 18 · see citing works
“Depression is notorious for being a risk factor for metabolic dysfunction associated with obesity, including an inflammatory response, high blood pressure, impaired insulin sensitivity, and impaired leptin sensitivity [11].”
BackgroundOn behalf of The By-Band-Sleeve Collaborating Group (2024) · BMJ Open · doi:10.1136/bmjopen-2022-071231 · Cited by 17 · see citing works
Inhibition of Pancreatic Lipase by Flavonoid Derivatives: In Vitro and In Silico Investigations
Tran, T., Mai, T. T., Ho, T.-T.-T., Le, T.-N.-D., Cao, T., Thai, K., & Tran, T.-S. (2024) · Advances in Pharmacological and Pharmaceutical Sciences · doi:10.1155/2024/6655996 · Cited by 18 · see citing works
“Scientifc investigations consistently elucidate a robust association between obesity and mental health issues, such as depression [10], anxiety [11], and low self-esteem [12].”
BackgroundAhmed, F., Arshad, M. T., Maqsood, S., Ikram, A., & Gnedeka, K. T. (2025) · Food Science & Nutrition · doi:10.1002/fsn3.70689 · Cited by 17 · see citing works
“Obese individuals tend to experience mood disorders, and individuals who experience anxiety or depression tend to gain weight, which is partly brought about by emotional eating and inactivity (Fulton et al. 2022; Dakanalis et al. 2023).”
Neural encoding of food and monetary reward delivery
Oren, S., Tittgemeyer, M., Rigoux, L., Schlamann, M. U., Schönberg, T., & Kuzmanovic, B. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.119335 · Cited by 18 · see citing works
“interplay between food intake, reward-related processing, gustatory processing, and homeostatic regulation have been suggested to underlie metabolic disorders such as obesity — and its severe medical and psychiatric comorbidities (Beutler et al., 2020; Fulton et al., 2021; Pantalone et al., 2017; Plassmann et al., 202…”
BackgroundSulaiman, S. K., Tsiga-Ahmed, F. I., Arora, T., Faris, M. E., Musa, M. S., Kareem, Y. A., Dayyab, F. M., Hussein, A., Sale, S., Javaid, S. F., et al. (2023) · Brain and Behavior · doi:10.1002/brb3.2990 · Cited by 20 · see citing works
“This is because obesity and being over-weight have been positively correlated to increased incidence of both anxiety and depression (Fulton et al., 2022; Sharafi et al., 2020).”
BackgroundWittekind, D. A., Kratzsch, J., Biemann, R., Mergl, R., Riedel-Heller, S. G., Witte, A. V., Villringer, A., & Kluge, M. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.891325 · Cited by 15 · see citing works
“A leptin analog, metreleptin, even exhibited swift antidepressant action in depressed anorexia-nervosa patients, which is associated with low leptin levels (65, 73).”
BackgroundChinese medicinal herbs as potential prodrugs for obesity
Law, S., Wang, Y., Lu, X., Au, D. C. T., Chow, W. Y. L., Leung, A. W., & Xu, C. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.1016004 · Cited by 15 · see citing works
“An abnormally accumulated fat is positively associated with diabetes, cardiovascular diseases, hyperlipidemia, hypertension, metabolic syndrome, fatty liver disease, a certain type of cancer, depression, and anxiety (Fulton et al., 2022).”
BackgroundLipids in major depressive disorder: new kids on the block or old friends revisited?
van der Heijden, A. R., & Houben, T. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1213011 · Cited by 15 · see citing works
“However, the relationship between obesity and depression seems rather bidirectional as underlying mechanisms are very closely intertwined (see the examples of inflammation and HPA-axis here above) (158, 162).”
BackgroundJing, X., Hong, F., Xie, Y., Xie, Y., Shi, F., Wang, R., Wang, L., Chen, Z., & Liu, X. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115796 · Cited by 16 · see citing works
Poly-Agonist Pharmacotherapies for Metabolic Diseases: Hopes and New Challenges
Allard, C., Cota, D., & Quarta, C. (2023) · Drugs · doi:10.1007/s40265-023-01982-6 · Cited by 15 · see citing works
“Psychological support before and after surgery is as important as metabolic monitoring, as following strict dietary guidelines can be difficult, especially for those who are more prone to anxiety-related problems [29].”
Wang, Y., Wang, H., Cheng, B., & Xia, J. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.04.134 · Cited by 16 · see citing works
Yan, L., & Li, J. (2022) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2022.04.015 · Cited by 16 · see citing works
Al-Amin, M., Rinky, F., Bhuiyan, M. N. H., Yeasmin, R., Akter, T., Hoque, N., & Reza, S. (2025) · BMJ Open · doi:10.1136/bmjopen-2024-097745 · Cited by 20 · see citing works
“108 The consumption patterns and dietary habits— including the intake of 6–8 food groups, as well as the consumption of wheat or rice, pulses, fats and oils, and sugar-sweetened foods and beverages—were significantly associated with the development of anxiety.”
Guo, J.-J., Hang, Q.-Q., Xu, T., Liang, W.-X., Gao, J.-K., Ou, H.-B., Jiang, F.-Z., Qiu, X.-C.-H., Tian, Z.-Z., Zhang, Y., et al. (2025) · Lipids in Health and Disease · doi:10.1186/s12944-025-02619-1 · Cited by 15 · see citing works
“Excess visceral fat promotes chronic inflammation via adipokine dysregulation and macrophage infiltration, exacerbating both periodontal and cardiovascular pathologies [13].”
Tsirmpas, C., Andrikopoulos, D., Fatouros, P., Eleftheriou, G., Anguera, J. A., Kontoangelos, K. A., & Papageorgiou, C. (2022) · Frontiers in Digital Health · doi:10.3389/fdgth.2022.868970 · Cited by 14 · see citing works
The prevalence of anxiety in adult endocrinology outpatients: A systematic review and meta–analysis
Kershaw, K. A., Storer, B., Braund, T. A., Chakouch, C., Coleshill, M. J., Haffar, S., Harvey, S. B., Newby, J. M., Sicouri, G., & Murphy, M. (2023) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2023.106357 · Cited by 16 · see citing works
Saffari, M., Lin, Y.-C., Huang, P., Huang, Y.-T., Huang, R.-Y., Huang, C. H., Chen, J., Poon, W. C., Griffiths, M. D., & Lin, C. (2024) · International Journal of Mental Health Promotion · doi:10.32604/ijmhp.2024.053432 · Cited by 14 · see citing works
“Moreover, psychological stress may concurrently be considered as one of the causes and outcomes of WS [8,20].”
BackgroundLiu, X., Xu, L., Luo, R., et al. (2022) · Journal of Food Processing and Preservation · doi:10.1111/jfpp.16528 · Cited by 14 · see citing works
Recent advances in biomimetic nanodelivery systems for the treatment of depression
Jiang, P., & Li, J. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.101781 · Cited by 16 · see citing works
“In the alarm phase, the internal balance of the organism is disrupted, and it begins to react to external stressors [42 – 44].”
Xanthine-induced deficits in hippocampal behavior and abnormal expression of hemoglobin genes
Kambe, J., Miyata, S., Li, C., Yamamoto, Y., & Nagaoka, K. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114476 · Cited by 13 · see citing works
Kozhuharov, V. R., Ivanov, K., Karcheva-Bahchevanska, D. P., Prissadova, N. A., & Ivanova, S. (2023) · Processes · doi:10.3390/pr11082337 · Cited by 13 · see citing works
Valenta, S. T., Stecchi, M., Perazza, F., Nuccitelli, C., Villanova, N., Pironi, L., Atti, A. R., & Petroni, M. L. (2023) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-023-01625-5 · Cited by 13 · see citing works
“Overall, the recurrent co-occurrence of obesity, anxiety-depressive syndromes, and the use of antidepressant therapies often results in a complex interplay, both in clinical presentation and adherence to treatment [37].”
BackgroundLonergan, C., Millar, S., & Kabir, Z. (2024) · PLoS ONE · doi:10.1371/journal.pone.0299029 · Cited by 18 · see citing works
Assessing the state of obesity care: Quality, access, guidelines, and standards
Kaplan, L. M., Apovian, C. M., Ard, J. D., Allison, D. B., Aronne, L. J., Batterham, R. L., Busetto, L., Dicker, D., Horn, D. B., Kelly, A. S., et al. (2024) · Obesity Science & Practice · doi:10.1002/osp4.765 · Cited by 14 · see citing works
“36 40 Endocrine dysfunctions, including hypogonadism, polycystic ovarian syndrome, and infertility, are common in patients with obesity, and low levels of sex steroids and growth hormone may exacerbate body composition abnormalities.”
BackgroundSchell, M., Wardelmann, K., Hauffe, R., Rath, M., Chopra, S., & Kleinridders, A. (2023) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2023.02.011 · Cited by 14 · see citing works
“The intake of an unhealthy high-calorie diet causes dysbiosis and is linked to altered emotional behavior in humans (20).”
BackgroundThe Melanocortin System: A Promising Target for the Development of New Antidepressant Drugs
Markov, D. D., Dolotov, O. V., & Grivennikov, I. A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24076664 · Cited by 14 · see citing works
“Indirectly, the possible involvement of the melanocortin system in depression is indicated by studies demonstrating a close relationship between depression and obesity [306,307].”
BackgroundLazarevich, I., Irigoyen‐Camacho, M. E., Vázquez, C. C. R., Tolentino, R. G., Velázquez-Alva, M. C., & Zepeda‐Zepeda, M. A. (2025) · Behavioral Sciences · doi:10.3390/bs15050669 · Cited by 13 · see citing works
“The bidirectional relationship between obesity and depression has been reported previously (Fulton et al., 2021; Vittengl, 2018), and anxiety is considered the most frequent condition related to unhealthy dietary patterns.”
Depression Following Acute Coronary Syndrome: A Review
Pan, R., Fan, Q., & Tao, R. (2023) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2409247 · Cited by 12 · see citing works
“sion, obesity and ACS are all associated with lifestyle risk factors, such as poor diet and physical inactivity [46].”
BackgroundLi, Y., Shi, N., & Tao, Y. (2025) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2025.1638381 · Cited by 11 · see citing works
Paraventricular ThalamicMC3RCircuits Link Energy Homeostasis with Anxiety-Related Behavior
Cho, D., O'Berry, K., Possa‐Paranhos, I. C., Butts, J., Palanikumar, N., & Sweeney, P. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.0704-23.2023 · Cited by 11 · see citing works
Zilkha, N., Chuartzman, S. G., Fishman, R., Ben‐Dor, S., & Kimchi, T. (2024) · Scientific Reports · doi:10.1038/s41598-024-70062-w · Cited by 12 · see citing works
Menichetti, F., Battezzati, A., Bertoli, S., Amicis, R. S. D., Foppiani, A., Sileo, F., & Leone, A. (2024) · European Journal of Clinical Nutrition · doi:10.1038/s41430-024-01536-3 · Cited by 11 · see citing works
“First, in fl ammation and oxidative stress are common among patients with anxiety or depression [44].”
Age and an obesogenic diet affect mouse behaviour in a sex‐dependent manner
Mort, E. J., Fordington, S., Heritage, S., Fowden, A. L., Jones, S., & Camm, E. J. (2023) · European Journal of Neuroscience · doi:10.1111/ejn.16070 · Cited by 11 · see citing works
“In particular, obesity is associated with increased anxiety (Fulton et al., 2022) and risk-taking behaviours in both adolescent and adult human populations (Ratcliff et al., 2011).”
Background
- Authors
- Fulton, S., Décarie-Spain, L., Fioramonti, X., Guiard, B., & Nakajima, S.
- Affiliations
- Centre Hospitalier de l’Université de Montréal (CA)
- Université de Bordeaux (FR)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Fulton, Stephanie
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2022-01
- Volume
- 33
- Issue
- 1
- Pages
- 18-35
- ISSN
- 1043-2760 (ISSN-L)
- OpenAlex
- W3213132689
- Semantic Scholar
- 7810f6a48f94176d175f9ea2f8ab49f150c84578
- Cited by
- 441
- References
- 173
- Citations by year
- 2026: 75 · 2025: 135 · 2024: 100 · 2023: 92 · 2022: 39
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- Oskar-Bordeaux (Universite de Bordeaux) (submittedVersion, cc-by-nc-nd)
- Funders
- Fonds de Recherche du Québec - Santé
- Japan Society for the Promotion of Science
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- obesity, depression, anxiety, neuroinflammation, insulin resistance, leptin resistance, visceral adipose tissue, hypertension, metabolic dysfunction, neuroimmune dysfunction, mood regulation
- MeSH terms
- Anxiety, Depression, Humans, Inflammation, Obesity, Prevalence
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
